The social construction of infant mortality: From grassroots to medicalization

Infant mortality as a problematic situation has been recognized for some 130 years in one form or another. It has undergone various changes in its empirical dimensions relative to whom we study within the population, what we study--low birth-weight vs. pre-term births--and how we study it--whether demographically or medically. An analysis of the process by which the condition was raised by claims makers as an intolerable situation among America's urban residents reveals that demographic and medical data were sparse. Nonetheless, a judgement about the meaning and significance of the condition was made, and that interpretation led to the promulgation of systems to both document and address the condition as it has come to be defined.^ This investigation depicts the historical context and natural history of infant mortality as one of a number of social problems that came to be defined through the interplay among groups and individuals making claims and how their claims came to the public policy agenda as worthy of collective resources--who won, who lost and why. The process of social definition focuses attention on the claims makers and the ways they contrast the meaning, origins and remedies for this troubling condition. The historical context becomes the frame of reference for understanding the actions of the claims makers and the meaning and significance they attached to the problem.^ We purport that "context" provides a closer reality than disjoined "value free" accounts. Context provides the evidence for the definition, who participated in the process, why and by what means.^ The role of women in the definitional process reveals the differences in approaches utilized by the women of the settlement house reform movement and African-American women working at the grass-roots. Much of the work done by these two groups provided options to the problem's remedy; however, their differences paved the way to our current (principally medically-oriented) definition and its inherent limitations. ^

For health's sake: Cervical and breast cancer screening

African-Americans make up twelve percent of the United States population, yet they experience morbidity and mortality at a rate that, in some cases, is disproportionate to their numbers. There are numerous health areas, including cancer, in which disparities exist. There are also numerous reasons which have been suggested to explain the high rates of cancer morbidity and mortality experienced by African-Americans. Among the reasons given to explain these differences are lack of knowledge and lack of access to medical care (1). This study sought to increase the knowledge, attitudes, and behavioral intentions of African-American women attending a Baptist church in Houston with regard to cervical cancer, breast cancer, Pap smear, and mammography. It was hypothesized that a church-based cancer education program would produce the desired change in knowledge, attitudes, and behavioral intentions.^ The quasi-experimental design of the study was untreated control group with pretest and posttest and untreated control group with posttest only. Female members of Mount Ararat Baptist Church took part in an eight-week, cancer education program based on social cognitive theory. Baseline data were collected before the start of the program at Mount Ararat and at Solid Rock Baptist Church, control group one. At the end of the program, the follow-up survey was administered at the program church, control church one, and in a third church, Damascus Missionary Baptist Church, which served as the posttest only group. The data were analyzed by Fisher's exact and paired t-test to determine if the program supported the project's hypotheses.^ Results of data analyses supported the major study hypotheses, the exception being behavioral intention to have Pap smear performed. Although the program appeared to have generally influenced changes in the desired direction, the results are limited due to the quasi-experimental design and small sample size. Longer term studies with larger sample sizes are needed to more fully develop and evaluate programs which impact the health of African-Americans. ^

A systematic review of the methods used to assess race and racial disparities in uterine fibroid research

Context: Black women are reported to have a higher prevalence of uterine fibroids, and a threefold higher incidence rate and relative risk for clinical uterine fibroid development as compared to women of other races. Uterine fibroid research has reported that black women experience greater uterine fibroid morbidity and disproportionate uterine fibroid disease burden. With increased interest in understanding uterine fibroid development, and race being a critical component of uterine fibroid assessment, it is imperative that the methods used to determine the race of research participants is defined and the operational definition of the use of race as a variable is reported for methodological guidance, and to enable the research community to compare statistical data and replicate studies. ^ Objectives: To systematically review and evaluate the methods used to assess race and racial disparities in uterine fibroid research. ^ Data Sources: Databases searched for this review include: OVID Medline, NML PubMed, Ebscohost Cumulative Index to Nursing and Allied Health Plus with Full Text, and Elsevier Scopus. ^ Review Methods: Articles published in English were retrieved from data sources between January 2011 and March 2011. Broad search terms, uterine fibroids and race, were employed to retrieve a comprehensive list of citations for review screening. The initial database yield included 947 articles, after duplicate extraction 485 articles remained. In addition, 771 bibliographic citations were reviewed to identify additional articles not found through the primary database search, of which 17 new articles were included. In the first screening, 502 titles and abstracts were screened against eligibility questions to determine citations of exclusion and to retrieve full text articles for review. In the second screening, 197 full texted articles were screened against eligibility questions to determine whether or not they met full inclusion/exclusion criteria. ^ Results: 100 articles met inclusion criteria and were used in the results of this systematic review. The evidence suggested that black women have a higher prevalence of uterine fibroids when compared to white women. None of the 14 studies reporting data on prevalence reported an operational definition or conceptual framework for the use of race. There were a limited number of studies reporting on the prevalence of risk factors among racial subgroups. Of the 3 studies, 2 studies reported prevalence of risk factors lower for black women than other races, which was contrary to hypothesis. And, of the three studies reporting on prevalence of risk factors among racial subgroups, none of them reported a conceptual framework for the use of race. ^ Conclusion: In the 100 uterine fibroid studies included in this review over half, 66%, reported a specific objective to assess and recruit study participants based upon their race and/or ethnicity, but most, 51%, failed to report a method of determining the actual race of the participants, and far fewer, 4% (only four South American studies), reported a conceptual framework and/or operational definition of race as a variable. However, most, 95%, of all studies reported race-based health outcomes. The inadequate methodological guidance on the use of race in uterine fibroid studies, purporting to assess race and racial disparities, may be a primary reason that uterine fibroid research continues to report racial disparities, but fails to understand the high prevalence and increased exposures among African-American women. A standardized method of assessing race throughout uterine fibroid research would appear to be helpful in elucidating what race is actually measuring, and the risk of exposures for that measurement. ^

Impact of racial differences in medical care on breast cancer survival: Findings from a large nationwide and retrospective cohort study

Background: No studies have attempted to determine whether nodal surgery utilization, time to initiation and completion of chemotherapy or surveillance mammography impact breast cancer survival. ^ Objectives and Methods: To determine whether receipt of nodal surgery, initiation and completion of chemotherapy, and surveillance mammography impact of racial disparities in survival among breast cancer patients in SEER areas, 1992-2005. ^ Results: Adjusting for nodal surgery did not reduce racial disparities in survival. Patients who initiated chemotherapy more than three months after surgery were 1.8 times more likely to die of breast cancer (95% CI 1.3-2.5) compared to those who initiated chemotherapy less than a month after surgery, even after controlling for known confounders or controlling for race. Despite correcting for chemotherapy initiation and completion and known predictors of outcome, African American women still had worse disease specific survival than their Caucasian counterparts. We found that non-whites underwent surveillance mammography less frequently compared with whites and mammography use during a one- or two-year time interval was associated with a small reduced risk of breast-cancer-specific and all-cause mortality. Women who received a mammogram during a two-year interval could expect the same disease-specific survival benefit or overall survival benefit as women who received a mammogram during a one-year interval. We found that while adjustment for surveillance mammography receipt and physician visits reduced differences in mortality between blacks and whites, these survival disparities were eliminated after adjusting for the number of surveillance mammograms received. ^ Conclusions: The disparities in survival among African American and Hispanic women with breast cancer are not explained by nodal surgery utilization or chemotherapy initiation and chemotherapy completion. Surveillance mammograms, physician visits and number of mammograms received may play a major role in achieving equal outcomes for breast cancer-specific mortality for women diagnosed with primary breast cancer. Racial disparities in all-cause mortality were explained by racial differences in surveillance mammograms to certain degree, but were no longer significant after controlling for differences in comorbidity. Focusing on access to quality care and post treatment surveillance might help achieve national goals to eliminate racial disparities in healthcare and outcomes. ^

Adherence to HIV /AIDS therapies among low -literacy populations: The ALP project

Adherence to HIV/AIDS therapies has been an important health problem since the early 1980s when AZT was first prescribed as a therapy for HIV/AIDS. It became particularly important between 1995 and 1997 with the advent of protease inhibitors (Chesney, Ickovics, Hecht, Sikipa, & Rabkin J., 1999) and became even more significant as persons with HIV/AIDS began to develop resistance to medications. Low-literacy populations have poorer health (Brez & Taylor, 1997) and higher AIDS rates (Simon, Hu, Diaz, & Kerndt, 1995), than their higher literacy counterparts due to delayed treatment (Baker, Parker, Williams, Clark, & Nurss, 1997), shame of literacy skills (Parikh, 1996), and poor access to care (Williams, et al., 1995). Poorer health and higher AIDS rates can also be attributed to poor patient-provider relationships (Crespo-Fierro, 1997; Eldred, Wu, Chaisson, & Moore, 1998) to a poorer understanding of medical protocols (Murphy, 1997), and inadequate patient education (Ungvarski, 1997; Davis, Michielutte, Askov, Williams, & Weiss, 1998, Doak, Doak, & Root, 1996). ^ The ALP intervention was developed for HIV positive low-literacy populations of African American women in Houston, Texas. The intervention was based on a needs assessment, using the PRECEDE model, an innovative process referred to as Intervention Mapping, and validated using formative evaluation methods with 54 individuals. The needs assessment resulted in a list of behavioral, environmental, predisposing, enabling, and reinforcing determinants of adherence. The Intervention Mapping framework was used to refine these determinants and develop a list of objectives describing what must be learned or changed to for the target population to adhere to HIV/AIDS therapies. Methods and strategies, were developed using theoretical constructs from the Health Belief Model (Rosenstock, 1974) and Social Cognitive Theory (Bandura, 1986). These theories, empirical evidence, and information from the target population indicated that perceived susceptibility, perceived severity, outcome expectations, and self-efficacy were important and changeable determinants of adherence to HIV/AIDS therapies for this population. ^ These components were brought together in the form of a theory-based color cartoon book and 10-minute cassette tape. The book was developed for people with 2.9 years of U.S. education as measured with the Flesch-Kincaid Grade Level method and the script was recorded onto a cassette tape to make it suitable for populations with even lower-literacy skills. A formative evaluation was conducted to ensure that the content and structure were accurate, clear, realistic, readable, appropriate, and likely to be used as intended. ^

Cervical cancer screening in Hispanic women as compared with other ethnic groups on an urban campus

Although Pap screening has decreased morbidity and mortality from cervical cancer, reported statistics indicate that among ethnic groups, Hispanic women are one of the least likely to follow screening guidelines. Human papillomavirus (HPV), a major risk factor for cervical cancer, as well as pre-cancerous lesions, may be detected by early Pap screening. With a reported 43% prevalence of HPV infection in college women, regular Pap screening is important. The purpose of this descriptive, cross-sectional survey was to examine self-reported cervical cancer screening rates in a target population of primarily Mexican-American college women, and to discover if recognized correlates for screening behavior explained differences in screening rates between this and two other predominant groups on the University of Houston Downtown campus, non-Hispanic white and African-American. The sample size consisted of 613 women recruited from summer 2003 classes. A survey, adapted from an earlier El Paso study, and based on constructs of the Health Belief Model (HBM), was administered to women ages 18 and older. It was found that although screening rates were similar across ethnic groups, overall, the Hispanic group obtained screening less frequently, though this did not reach statistical significance. However, a significant difference in lower screening rates was found in Mexican American women ages <25. Additionally, of the predicted correlates, the construct of perceived barriers from the HBM was most significant for the Mexican American group for non-screening. For all groups, knowledge about cervical cancer was negatively correlated with ever obtaining Pap screening and screening within the past year. This implies that if health counseling is given at the time of women's screening visits, both adherence to appropriate screening intervals and risk factor avoidance may be more likely. Studies such as these are needed to address both screening behaviors and likelihood of follow-up for abnormal results in populations of multicultural, urban college women. ^

Impact of oral contraceptives on weight, body composition, and cardiovascular disease risk factors in women age 18--30 years participating in a 15-week exercise program

Objective. To assess differences in body weight, body composition, total cholesterol, blood pressure, and blood glucose between OC users and non-users age 18-30 y before and after a 15-week cardiovascular exercise program in Houston, TX from 2003 to 2007.^ Study Design. Secondary analysis of prospective data. ^ Study Subjects. 453 Non-Hispanic white (NHW), Hispanic, and African American (AA) women age 18-30 y with no previous live birth, a history of menstruating, no use of other hormonal contraceptives or medications, no menopause or hysterectomy, and no current pregnancies.^ Measurements. Demographic data, medication use, and menstrual history were assessed via self-administered questionnaires at baseline. Anthropometric and laboratory measures were taken at baseline and 15-weeks. ^ Data Analysis. Linear regression assessed the association between OC use and study variables at baseline, and the change in study variables from baseline to 15-weeks. Logistic regression assessed the association between OC use and CVD risk. Each analysis was also stratified by race/ethnicity. ^ Results. At baseline, OC users had higher total cholesterol (p<.0005) and were above cholesterol risk cut points for CVD (OR=4.3, 95% CI=2.4-7.7) compared to non-users. At baseline, OC use was also associated with higher diastolic blood pressure (p=.018) compared to non-users, primarily in non-Hispanic whites (p=.007). OC use was associated with lower blood glucose compared to non-users in Hispanics only (p=.008). OC use was associated with absolute change in diastolic blood pressure (p=.044) and total cholesterol (p=.003). There was evidence that OC use may affect individuals differently based on race/ethnicity for certain obesity and CVD risk factors.^ Conclusions. OC users and non-users responded similarly to a 15-week cardiovascular exercise program. Exceptions included a greater change in diastolic blood pressure and total cholesterol among NHW and Hispanic OC users compared to non-users after exercise intervention. At baseline, OC use was associated with diastolic blood pressure and was most strongly associated with increased levels of total cholesterol. OC users were at greater risk of having total cholesterol above CVD risk cut points than non-users.^

Demographics of having a gun in the home in Columbia, SC as reported by women primary care patients

Objectives. To determine demographic correlates of having one or more guns in the household of women primary care patients in the southern USA. ^ Methods. All participants in this cross-sectional study were women aged 18-65 who were insured by either Medicaid or a managed care provider and had ever had an intimate sexual relationship with a male partner that lasted at least three months. Prevalence rate ratios and 95% confidence intervals were calculated using stratified analyses for having a gun in the home and the following demographic factors: age, race, educational attainment, marital status, employment status, and alcohol/drug use. ^ Results. Twenty six percent of households had at least one gun and 6.5% had 3 or more guns. The following demographic characteristics of women were associated with having a gun in the household: age (>40) (prevalence rate ratio [PRR] = 1.4; 95% confidence interval [CI] = 1.1–1.8); White race (PRR = 1.89; 95% CI = 1.61–2.27); currently being employed (PRR = 1.72; 95% CI = 1.22–2.44); higher education; and being insured by an HMO (PRR = 1.92; 95% CI = 1.47–2.50). Neither the partner's unemployment nor his substance use was associated with having a gun. While White households were more likely to have a gun, the same correlates of gun ownership held for both White and African-American households; being married or living as married and higher socio-economic status (i.e. HMO insurance and being employed) were strongly correlated with gun in the household. The following were correlated with having multiple guns in the household: White race (p < 0.0001); increased age (p = 0.005); being currently married or living as married (p < 0.0001); and HMO insured status (p < 0.0001). Among those households with at least one gun, White race and married or currently living as married were associated with having 2 or more guns relative to one gun in the household. ^ Conclusions. Currently living with a man and being of higher socio-economic status were strong correlates of household gun ownership among both Whites and African-Americans. Substance use was not associated with household gun ownership. ^

Lifetime changes in body mass index and risk of breast cancer in minority women

Introduction: Obesity is an epidemic in the United States, especially among Hispanics and African-Americans. Studies of obesity and breast cancer risk and subtype have been conducted primarily in non-Hispanic whites. Obesity is inversely associated with premenopausal breast cancer, but both obesity and weight gain increase the risk of postmenopausal disease. Obesity has been associated with breast cancer subtype in many studies. Methods: To assess the association between changes in body mass index (BMI) over the lifetime, weight gain, and breast cancer in Mexican-American women, we conducted a case-control study using 149 cases and 330 age-matched controls. In a second study, we identified 212 African-American and 167 Mexican-American women with breast cancer in the ongoing ELLA Bi-National Breast Cancer Study, abstracted medical charts to classify tumors as ER+/PR+, HER2+, or ER-/PR-/HER2-, and assessed the association between lifetime changes in body mass index, weight gain, and breast cancer subtype. In both studies, growth mixture modeling was use to identify trajectories of change in BMI over the lifetime, and these trajectories were used as exposures in a logistic regression model to calculate odds ratios (OR). Results: There was no association between trajectories of change in BMI and breast cancer risk in Mexican-American women. In addition, BMI at ages 15 and 30 and at diagnosis was not associated with breast cancer. However, adult weight gain was inversely associated with breast cancer risk (per 5kg, OR=0.92, 95% CI: 0.85-0.99). The case-only analysis found no association between obesity at ages 15 and 30 and at diagnosis and breast cancer subtype. Further, there was no association between adult weight gain (defined as weight change from age 15 to time of diagnosis) and breast cancer subtype. Conclusions: Obesity was not associated with breast cancer risk in Mexican-American women, while adult weight gain reduced the risk independently of menopausal status. These results are contradictory of those in non-Hispanic white women and suggest that the etiology of breast cancer may differ by race/ethnicity. Further, obesity was not associated with breast cancer subtype in African-American and Mexican-American women, contrary to results in non-Hispanic white women. ^

Changes in sexual behaviors associated with crack cocaine cessation among African Americans in Houston, Texas

Aim To examine the association between the crack cocaine cessation and risky sexual behaviors. Design and setting Between June 2002 and March 2005, a sample of African-American residents of Houston, Texas who were using crack at the time of enrollment participated in a cohort study to evaluate per outreach interventions to reduce HIV risk behaviors. The sample for this study consisted of 351 women and men who completed structured surveys at baseline and at six months about socio-demographic characteristics, drug use, and sexual behaviors. Multivariate logistic regression was used to analyze the association between crack cessation and risky sexual behaviors at follow-up, while controlling for confounding characteristics. Measurements Crack cessation was defined as reporting no crack use in the 30 days prior to the follow-up interview. Possible associated factors included unprotected sex, having multiple sex partners, trading sex for money/drugs, crack use, and socio-demographic variables. Findings At the six-month follow-up interview, 21% of participants reported that they had not used crack in the previous 30 days. For women, crack cessation was significantly associated with having only one sex partner at follow-up; for men, crack cessation was significantly associated with being single, separated, or divorced at baseline, having only one sex partner at follow-up, and initiating protected sex by follow-up. Conclusion These findings support previous research indicating that crack use is associated with unprotected sex and multiple sexual partners, as men and women who ceased crack use were less likely to engage in these risky sexual behaviors. Findings demonstrate that treatment for crack use could have a meaningful effect on risky sexual behaviors and HIV/STI prevention.^

Systematic review of current trends of cardiovascular disease (CVD) and association between health insurance coverage and CVD mortality among women aged 60--65 in Texas in 2000--2011

Cardiovascular disease (CVD) is highly preventable, yet it is a leading cause of death among women in Texas. The primary goals of this research were to examine past and current trends of CVD, as well as identify whether there is an association between the insurance coverage and mortality from CVD among women aged 60–65 in Texas between 2000 and 2011. ^ The systematic review of the research is based on the guidelines and recommendations set by the Centre for Reviews and Dissemination for conducting reviews in health care. Over 47 citations of peer-reviewed articles from Ovid MEDLINE and PubMed databases and five websites were identified, of which 7 studies met inclusion criteria for the first systematic review to examine the trends of CVD in Texas. Ten citations of peer-reviewed articles from Ovid MEDLINE and PubMed databases and five web sites were reviewed for the second systematic review (to study the association between insurance coverage and cardiovascular health among Texas women 60–64 years of age), of which 3 studies met inclusion criteria and were included in the research. The results of the study highlighted key gaps in the existing literature and important areas for the further research, as well as determined directions for future public health CVD prevention programs in Texas. ^ Based on the conducted research, the major determinants of premature mortality among women attributed to cardiovascular disease are based on individual level characteristics, more specifically sex, age, race/ethnicity, and education. The results indicate that African American and non-Hispanic white women are more likely to have higher CVD mortality rates than Hispanic women due to higher prevalence of cardiac risk factors. The data also shows higher levels of mortality from CVD in the southeastern United States, with Texas ranking as the third state with the highest prevalence of CVD among women. According to the Texas Department of State Health Services, there are approximately 56,000 deaths caused by CVD annually in Texas, which represents about one death every ten minutes. Coronary artery disease and stroke were the causes of 31.2 percent of all female deaths in Texas in 2009, meaning that approximately 68 women die from any form of cardiac disease in Texas each day. ^ The data of the reviewed studies indicate that women' lack of health insurance was significantly associated with a higher prevalence of cardiovascular disease. The uninsured women were more likely to be unaware of their risk factors and more likely to have undiagnosed diabetes—a co-morbidity factor of CVD. One of the studies also reports strong correlation between state rates of uninsured and lower rates of preventive care. Given these strong correlations, those who were chronically uninsured were at a higher risk of mortality than the insured, due to prolonged periods of time without basic access to preventive and medical care. ^ Suggested recommendations to decrease CVD mortality rates in Texas are consistent with the existing literature and include state policy development that addresses elimination of health disparities, consideration of potential benefits of universal health coverage by the legislative policymakers, and maintenance of solid partnerships between public health agencies and hospitals to educate on, diagnose, and treat CVD among the female population in Texas. ^

Characteristics of a spina bifida population including North American Caucasian and Hispanic individuals.

BACKGROUND: Meningomyelocele (MM) is a common human birth defect. MM is a disorder of neural development caused by contributions from genes and environmental factors that result in the NTD and lead to a spectrum of physical and neurocognitive phenotypes. METHODS: A multidisciplinary approach has been taken to develop a comprehensive understanding of MM through collaborative efforts from investigators specializing in genetics, development, brain imaging, and neurocognitive outcome. Patients have been recruited from five different sites: Houston and the Texas-Mexico border area; Toronto, Canada; Los Angeles, California; and Lexington, Kentucky. Genetic risk factors for MM have been assessed by genotyping and association testing using the transmission disequilibrium test. RESULTS: A total of 509 affected child/parent trios and 309 affected child/parent duos have been enrolled to date for genetic association studies. Subsets of the patients have also been enrolled for studies assessing development, brain imaging, and neurocognitive outcomes. The study recruited two major ethnic groups, with 45.9% Hispanics of Mexican descent and 36.2% North American Caucasians of European descent. The remaining patients are African-American, South and Central American, Native American, and Asian. Studies of this group of patients have already discovered distinct corpus callosum morphology and neurocognitive deficits that associate with MM. We have identified maternal MTHFR 667T allele as a risk factor for MM. In addition, we also found that several genes for glucose transport and metabolism are potential risk factors for MM. CONCLUSIONS: The enrolled patient population provides a valuable resource for elucidating the disease characteristics and mechanisms for MM development.

Adolescent tobacco use: Studies of prevalence, factorial validity, and factorial invariance between African Americans and Whites

In the last thirty years, increasing efforts have been made to reduce the prevalence of adolescent tobacco use in the United States. Although the prevalence has declined dramatically over the past decade, there are still sharp differences in adolescent smoking-initiation rates across racial/ethnic groups. Large-scale surveys frequently assess smoking-related attitudes, self-efficacy, and intentions to explain the differences in smoking rates between African Americans and Whites. However, there is little agreement about which constructs are significant. Moreover, the psychometric properties of smoking-related attitude, self-efficacy, and intention constructs have not been fully examined. More studies are needed to understand existing patterns of tobacco use and to validate and fully exploit the constructs' relationship to adolescent smoking initiation across racial/ethnic groups. ^ This dissertation reports on a secondary analysis of data from a large multi-ethnic convenience sample of sixth- through eighth-grade students in 22 schools in East Texas and the city of Houston. The specific aims of this dissertation were to (1) describe smoking and alternate tobacco product use rates by race/ethnicity, gender, age, and grade level (Article 1); (2) test the factorial validity of smoking-related attitudes, self-efficacy, and intentions using confirmatory factor analysis techniques (Article 2); and (3) test the factorial invariance of smoking-related attitudes, self-efficacy, and intentions between African Americans and Whites (Article 3). ^ The prevalence findings confirm the disparities in tobacco use among African American, Hispanic, and White adolescents that other surveys have reported (Article 1). This study also demonstrates the usefulness of examining use patterns of not only cigarettes but also alternative tobacco products in younger multiethnic populations, as well as of providing epidemiological data estimates about different phases of smoking. The confirmatory factor analysis provides evidence of construct validity of attitude, self-efficacy, and intention scales for the multiethnic sample (Article 2). Finally, the factorial invariance analyses indicates that some measures representing smoking-related attitudes, self-efficacy, and intentions may not be appropriate for use among both African Americans and Whites (Article 3). Additional research is needed to further our understanding of the patterns and predictors of youth tobacco use initiation. ^

Adiposity and the perilipin gene: The role of single locus and multilocus variation, obesity-related quantitative traits, and disease-related phenotypes in the Atherosclerosis Risk in Communities (ARIC) study

Obesity is a complex multifactorial disease and is a public health priority. Perilipin coats the surface of lipid droplets in adipocytes and is believed to stabilize these lipid bodies by protecting triglyceride from early lipolysis. This research project evaluated the association between genetic variation within the human perilipin (PLIN) gene and obesity-related quantitative traits and disease-related phenotypes in Non-Hispanic White (NHW) and African American (AA) participants from the Atherosclerosis Risk in Communities (ARIC) Study. ^ Multivariate linear regression, multivariate logistic regression, and Cox proportional hazards models evaluated the association between single gene variants (rs2304794, rs894160, rs8179071, and rs2304795) and multilocus variation (rs894160 and rs2304795) within the PLIN gene and both obesity-related quantitative traits (body weight, body mass index [BMI], waist girth, waist-to-hip ratio [WHR], estimated percent body fat, and plasma total triglycerides) and disease-related phenotypes (prevalent obesity, metabolic syndrome [MetS], prevalent coronary heart disease [CHD], and incident CHD). Single variant analyses were stratified by race and gender within race while multilocus analyses were stratified by race. ^ Single variant analyses revealed that rs2304794 and rs894160 were significantly related to plasma triglyceride levels in all NHWs and NHW women. Among AA women, variant rs8179071 was associated with triglyceride levels and rs2304794 was associated with risk-raising waist circumference (>0.8 in women). The multilocus effects of variants rs894160 and rs2304795 were significantly associated with body weight, waist girth, WHR, estimated percent body fat, class II obesity (BMI ≥ 35 kg/m2), class III obesity (BMI ≥ 35 kg/m2), and risk-raising WHR (>0.9 in men and >0.8 in women) in AAs. Variant rs2304795 was significantly related to prevalent MetS among AA males and prevalent CHD in NHW women; multilocus effects of the PLIN gene were associated with prevalent CHD among NHWs. Rs2304794 was associated with incident CHD in the absence of the MetS among AAs. These findings support the hypothesis that variation within the PLIN gene influences obesity-related traits and disease-related phenotypes. ^ Understanding these effects of the PLIN genotype on the development of obesity can potentially lead to tailored health promotion interventions that are more effective. ^

Dysregulation of alternative splicing of coagulation factor V results in bleeding disorder, east Texas type and other disorders of hemostasis

The studies completed herein explore different phenotypes related to the genetic defects that predispose individuals to a disruption of normal hemostasis. In the first study, a novel autosomal dominant bleeding disorder, which is characterized by excessive bleeding with trauma or surgery and menorrhagia in affected women, was studied in a large family (16 affected individuals) from east Texas. Affected members had a prolongation of their PT and/or aPTT, but normal clinical coagulation studies. Previous linkage analysis by Kuang et. al. (2001) mapped the defective gene to 1g23-24 (LODmax 7.22), which contains the gene for coagulation factor V (FV). I identified an alteration (A2440G) in the FV gene in exon 13 that segregated with the disease and was not present in 62 controls. Interestingly, this alteration resulted in a 22-fold up-regulation of a novel alternative splicing variant in patients' RNA versus controls. This translated into a similar fold increase in a 250-kDa isoform of FV seen in patients' plasma versus controls. A recombinant of this splicing event exhibited an increased sensitivity to cleavage by activated protein C (APC) that was more striking in the presence of PS. In addition, this novel isoform had increased APC cofactor activity, thus increasing the degradation of FVIIIa. These data indicated that A2440G up-regulates an alternatively spliced transcript of FV, and increases a FV isoform that hinders coagulation as opposed to promoting it like its wild-type counterpart. ^ The second study reports the largest screening to date of African Americans in two independent cohorts for a rare prothrombin variant, C20209T, which is suspected to be associated with thrombotic disease. The Texas Medical Center Genetics Resource (TexGen) Stroke DNA repository revealed 1.67% (Fisher p=0.27) of African American stroke patients were heterozygous for the 20209*T allele. Screening of the Atherosclerosis Risk in Communities Study (ARIC) cohort (n=3470) for the 20209*T allele revealed a population prevalence of 0.58% in individuals of African American descent; however, all associations with thrombotic disease were negative. Analysis of these two independent cohorts revealed that, unlike its neighbor G20210A, the C20209T variant does not increase the risk of thrombotic events in the African American population. ^