Linkage and association of candidate obesity genes in Mexican-Americans from Starr County, Texas

Obesity and related chronic diseases represent a tremendous public health burden among Mexican Americans, a young and rapidly-expanding population. This study investigated the impact of variation within eight candidate obesity genes, which include leptin (LEP), leptin receptor (LEPR), neuropeptide Y (NPY), NPYY1 receptor (NPYY1), glucagon-like peptide-1 (GLP-1), GLP-1 receptor (GLP1R), beta-3 adrenergic receptor (β3AR), and uncoupling protein (UCP1), on variation in human obesity status and/or quantitative traits related to obesity in Mexican Americans from Starr County, Texas. The Trp64Arg polymorphism within β3AR was typed in 820 random individuals and 240 pedigrees (N = 2,044). The Arg allele frequency was significantly greater in obese versus non-obese individuals (0.20 versus 0. 15, respectively). In addition, within the random sample, the Arg allele was associated with significantly greater body weight (p = 0.031) and body mass index (BMI, p = 0.008) than the Trp allele. In the family sample, the Trp64Arg locus was also linked to percent fat (p = 0.045) but not to body weight or BMI. No linkage between obesity, diabetes, hypertension, or gallbladder disease and the Trp64Arg mutation was observed in families using affected sib pair linkage analysis or the transmission disequilibrium test. Microsatellite markers proximate to the remaining seven genes were typed in 302 individuals from 59 families. Sib pair linkage analysis provided evidence for linkage between obesity and NPY within affected sibling pairs (p = 0.042; n = 170 pairs). NPY was also linked to weight (p = 0.020), abdominal circumference (p = 0.031), hip circumference (p = 0.012), DBP (p ≤ 0.005), and a composite measure of body mass/fat (p ≤ 0.048) in all sibling pairs (n = 545 pairs). Additionally, LEP was linked to waist/hip ratio (p ≤ 0.009), total cholesterol (p ≤ 0.030), and HDL cholesterol (p ≤ 0.026), and LEPR was linked to fasting blood glucose (p ≤ 0.018) and DBP (p ≤ 0.003). Subsequent to the linkage analyses, the NPY gene was sequenced and eight variant sites identified. Two variant sites (-880I/D and 69I/D) were typed in a random sample of 914 individuals. The 880I/D variant was significantly associated with waist/hip ratio (p = 0.035) in the entire sample (N = 914) and with BMI (p = 0. 031), abdominal circumference (p = 0.044), and waist/hip ratio (p = 0.041) in a non-obese subsample (BW < 30 kg/m2, n = 594). The 69I/D variant was a rare mutation observed in only one pedigree and was not associated with obesity or body size/mass within this pedigree. Results of this study indicate that variation at or near β3AR, LEP, LEPR, and NPY may exert effects which increase obesity susceptibility and influence obesity-related measures in this population. ^

Towards the identification of a tumor suppressor gene on chromosome 3p12: Physical mapping and candidate gene screening

Renal cell carcinoma (RCC) is the most common malignant tumor of the kidney. Characterization of RCC tumors indicates that the most frequent genetic event associated with the initiation of tumor formation involves a loss of heterozygosity or cytogenetic aberration on the short arm of human chromosome 3. A tumor suppressor locus Nonpapillary Renal Carcinoma-1 (NRC-1, OMIM ID 604442) has been previously mapped to a 5–7 cM region on chromosome 3p12 and shown to induce rapid tumor cell death in vivo, as demonstrated by functional complementation experiments. ^ To identify the gene that accounts for the tumor suppressor activities of NRC-1, fine-scale physical mapping was conducted with a novel real-time quantitative PCR based method developed in this study. As a result, NRC-1 was mapped within a 4.6-Mb region defined by two unique sequences within UniGene clusters Hs.41407 and Hs.371835 (78,545Kb–83,172Kb in the NCBI build 31 physical map). The involvement of a putative tumor suppressor gene Robo1/Dutt1 was excluded as a candidate for NRC-1. Furthermore, a transcript map containing eleven candidate genes was established for the 4.6-Mb region. Analyses of gene expression patterns with real-time quantitative RT-PCR assays showed that one of the eleven candidate genes in the interval (TSGc28) is down-regulated in 15 out of 20 tumor samples compared with matched normal samples. Three exons of this gene have been identified by RACE experiments, although additional exon(s) seem to exist. Further gene characterization and functional studies are required to confirm the gene as a true tumor suppressor gene. ^ To study the cellular functions of NRC-1, gene expression profiles of three tumor suppressive microcell hybrids, each containing a functional copy of NRC-1, were compared with those of the corresponding parental tumor cell lines using 16K oligonucleotide microarrays. Differentially expressed genes were identified. Analyses based on the Gene Ontology showed that introduction of NRC-1 into tumor cell lines activates genes in multiple cellular pathways, including cell cycle, signal transduction, cytokines and stress response. NRC-1 is likely to induce cell growth arrest indirectly through WEE1. ^

Psychosocial and environmental predictors of calcium intake, physical activity and bone health among adolescent girls

Objectives. The purpose of this study was to identify the psychosocial and environmental predictors and the pathways they use to influence calcium intake, physical activity and bone health among adolescent girls. Methods. A secondary data analysis using a cross-sectional and longitudinal study design was implemented to examine the associations of interest. Data from the Incorporating More Physical Activity and Calcium in Teens (IMPACT) study collected in 2001-2003 were utilized for the analyses. IMPACT was a 1½ year nutrition and physical activity intervention study conducted among 718 middle-school girls in central Texas. Hierarchical regression modeling and Structural Equation Modeling (SEM) were used to determine the psychosocial predictors of calcium intake, physical activity and bone health at baseline. Hierarchical regression was used to determine if psychosocial factors at baseline were significant predictors of calcium intake and physical activity at follow-up. Data was adjusted for included BMI, lactose intolerance, ethnicity, menarchal status, intervention and participation in 7th grade PE/athletics. Results. Results of the baseline regression analysis revealed that calcium self-efficacy and milk availability at home were the strongest predictors of calcium intake. Friend engagement in physical activity, physical activity self-efficacy and participation in sports teams were the strongest predictors of physical activity. Finally, physical activity outcome expectations, social support and participation in sports teams were significant predictors of stiffness index at baseline. Results of the baseline SEM path analysis found that outcome expectations and milk availability at home directly influenced calcium intake. Knowledge and calcium self-efficacy indirectly influenced calcium intake with outcome expectations as the mediator. Physical activity self-efficacy and social support had significant direct and indirect influence on physical activity with participation in sports teams as the mediator. Participation in sports teams had a direct effect on both physical activity and stiffness index. Results of regression analysis for baseline predicting follow-up showed that participation in sports teams, self-efficacy, outcome expectations and social support at baseline were significant predictors of physical activity at follow-up. Conclusion. Results of this study reinforce the relevance of addressing both, psychosocial and environmental factors which are critical when developing interventions to improve bone health among adolescent girls. ^

The effects of ethnicity and ethnic composition of schools on physical activity and nutrition behaviors of 8th and 11th graders in Texas

With rates of obesity and overweight continuing to increase in the US, the attention of public health researchers has focused on nutrition and physical activity behaviors. However, attempts to explain the disparate rates of obesity and overweight between whites and Hispanics have often proven inadequate. Indeed, the nebulous term ‘ethnicity’ provides little important detail in addressing potential biological, behavioral, and environmental factors that may affect rates of obesity and overweight. In response to this, the present research seeks to test the explanatory powers of ethnicity by situating the nutrition and physical activity behaviors of whites and Hispanic into their broader social contexts. It is hypothesized that a student's gender and grade level, as well as the socioeconomic status and ethnic composition of their school, will have more predictive power for these behaviors than will self-reported ethnicity. ^ Analyses revealed that while ethnicity did not seem to impact nutrition behaviors among the wealthier schools and those with fewer Hispanics, ethnicity was relevant in explaining these behaviors in the poorest tertile of schools and those with the highest number of Hispanics. With respect to physical activity behaviors, the results were mixed. The variables representing regular physical activity, participation in extracurricular physical activities, and performance of strengthening and toning exercises were more likely to be determined by SES and ethnic composition than ethnicity, especially among 8th grade males. However, school sports team and physical education participation continued to vary by ethnicity, even after controlling for SES and ethnic composition of schools. In conclusion then, it is important to understand the intersecting demographic and social variables that define and surround the individual in order to understand nutrition and physical activity behaviors and thus overweight and obesity.^

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. ^

Baseline evaluation of environmental physical activity and nutrition support of Texas Medical Center hospital worksites

Background: Obesity is a major health problem in the United States that has reached epidemic proportions. With most U.S adults spending the majority of their waking hours at work, the influence of the workplace environment on obesity is gaining in importance. Recent research implicates worksites as providing an 'obesogenic' environment as they encourage overeating and reduce the opportunity for physical activity. Objective: The aim of this study is to describe the nutrition and physical activity environment of Texas Medical Center (TMC) hospitals participating in the Shape Up Houston evaluation study to develop a scoring system to quantify the environmental data collected using the Environmental Assessment Tool (EAT) survey and to assess the inter-observer reliability of using the EAT survey. Methods: A survey instrument that was adapted from the Environmental Assessment Tool (EAT) developed by Dejoy DM et al in 2008 to measure the hospital environmental support for nutrition and physical activity was used for this study. The inter-observer reliability of using the EAT survey was measured and total percent agreement scores were computed. Most responses on the EAT survey are dichotomous (Yes and No) and these responses were coded with a '0' for a 'no' response and a '1' for a 'yes' response. A summative scoring system was developed to quantify these responses. Each hospital was given a score for each scale and subscale on the EAT survey in addition to a total score. All analyses were conducted using Stata 11 software. Results: High inter-observer reliability is observed using EAT. The percentage agreement scores ranged from 94.4%–100%. Only 2 of the 5 hospitals had a fitness facility onsite and scores for exercise programs and outdoor facilities available for hospital employees ranged from 0–62% and 0–37.5%, respectively. The healthy eating percentage for hospital cafeterias range from 42%–92% across the different hospitals while the healthy vending scores were 0%–40%. The total TMC 'healthy hospital' score was 49%. Conclusion: The EAT survey is a reliable instrument for measuring the physical activity and nutrition support environment of hospital worksites. The study results showed a large variability among the TMC hospitals in the existing physical activity and nutrition support environment. This study proposes cost effective policy changes that can increase environmental support to healthy eating and active living among TMC hospital employees.^