Mutual Information for Testing Gene-Environment Interaction

Despite current enthusiasm for investigation of gene-gene interactions and gene-environment interactions, the essential issue of how to define and detect gene-environment interactions remains unresolved. In this report, we define gene-environment interactions as a stochastic dependence in the context of the effects of the genetic and environmental risk factors on the cause of phenotypic variation among individuals. We use mutual information that is widely used in communication and complex system analysis to measure gene-environment interactions. We investigate how gene-environment interactions generate the large difference in the information measure of gene-environment interactions between the general population and a diseased population, which motives us to develop mutual information-based statistics for testing gene-environment interactions. We validated the null distribution and calculated the type 1 error rates for the mutual information-based statistics to test gene-environment interactions using extensive simulation studies. We found that the new test statistics were more powerful than the traditional logistic regression under several disease models. Finally, in order to further evaluate the performance of our new method, we applied the mutual information-based statistics to three real examples. Our results showed that P-values for the mutual information-based statistics were much smaller than that obtained by other approaches including logistic regression models.

Symmetric inverse consistent nonlinear registration driven by mutual information.

A nonlinear viscoelastic image registration algorithm based on the demons paradigm and incorporating inverse consistent constraint (ICC) is implemented. An inverse consistent and symmetric cost function using mutual information (MI) as a similarity measure is employed. The cost function also includes regularization of transformation and inverse consistent error (ICE). The uncertainties in balancing various terms in the cost function are avoided by alternatively minimizing the similarity measure, the regularization of the transformation, and the ICE terms. The diffeomorphism of registration for preventing folding and/or tearing in the deformation is achieved by the composition scheme. The quality of image registration is first demonstrated by constructing brain atlas from 20 adult brains (age range 30-60). It is shown that with this registration technique: (1) the Jacobian determinant is positive for all voxels and (2) the average ICE is around 0.004 voxels with a maximum value below 0.1 voxels. Further, the deformation-based segmentation on Internet Brain Segmentation Repository, a publicly available dataset, has yielded high Dice similarity index (DSI) of 94.7% for the cerebellum and 74.7% for the hippocampus, attesting to the quality of our registration method.

Household Hardships, Public Programs, and Their Associations with the Health and Development of Very Young Children: Insights from Children’s HealthWatch

America’s low-income families struggle to protect their children from multiple threats to their health and growth. Many research and advocacy groups explore the health and educational effects of food insecurity, but less is known about these effects on very young children. Children’s HealthWatch, a group of pediatric clinicians and public health researchers, has continuously collected data on the effects of food insecurity alone and in conjunction with other household hardships since 1998. The group’s peer reviewed research has shown that a number of economic risks at the household level, including food, housing and energy insecurity, tend to be correlated. These insecurities alone or in conjunction increase the risk that a young child will suffer various negative health consequences, including increases in lifetime hospitalizations, parental report of fair or poor health,1 or risk for developmental delays.2 Child food insecurity is an incremental risk indicator above and beyond the risk imposed by household-level food insecurity. The Children’sHealthwatch research also suggests public benefits programs modify some of these effects for families experiencing hardships. This empirical evidence is presented in a variety of public venues outside the usual scientific settings, such as congressional hearings, to support the needs of America’s most vulnerable population through policy change. Children’s HealthWatch research supports legislative solutions to food insecurity, including sustained funding for public programs and re-evaluation of the use of the Thrifty Food Plan as the basis of SNAP benefits calculations. Children’s HealthWatch is one of many models to support the American Academy of Pediatrics’ call to “stand up, speak up, and step up for children.”3 No isolated group or single intervention will solve child poverty or multiple hardships. However, working collaboratively each group has a role to play in supporting the health and well-being of young children and their families. 1. Cook JT, Frank DA, Berkowitz C, et al. Food insecurity is associated with adverse health outcomes among human infants and toddlers. J Nutr. 2004;134:1432-1438. 2. Rose-Jacobs R, Black MM, Casey PH, et al. Household food insecurity: associations with at-risk infant and toddler development. Pediatrics. 2008;121:65-72. 3. AAP leader says to stand up, speak up, and step up for child health [news release]. Boston, MA: American Academy of Pediatrics; October 11, 2008. http://www2.aap.org/pressroom/nce/nce08childhealth.htm. Accessed January 1, 2012.

Commentary on "Household Hardships, Public Programs, and Their Associations with the Health and Development of Very Young Children: Insights from Children's HealthWatch"

This commentary, written in response to the article "Household Hardships, Public Programs, and Their Associations with the Health and Development of Very Young Children: Insights from Children's HealthWatch", highlights the importance of the research done by Children's HealthWatch in relation to childhood food insecurity. Childhood food insecurity has been linked with various adverse health effects, including undernutrition, poor or delayed child development, and social and psychological consequences. Children's HealthWatch provides important data that can be used to monitor threats to our children's well-being and address problems with effective interventions.

The angiotensin-converting enzyme insertion/deletion polymorphism and its associations with carotid artery wall thickness and coronary heart disease: The atherosclerosis risk in communities study

Coronary heart disease (CHD) is the leading cause of death in the United States. Recently, renin-angiotensin system (RAS) was found associated with atherosclerosis formation, with angiotensin II inducing vascular smooth muscle cell growth and migration, platelet activation and aggregation, and stimulation of plasminogen activator inhibitor-1. Angiotensin II is converted from angiotensin I by angiotensin I-converting enzyme (ACE) and this enzyme is mainly genetically determined. The ACE gene has been assigned to chromosome 17q23 and an insertion/deletion (I/D)polymorphism has been characterized by the presence/absence of a 287 bp fragment in intron 16 of the gene. The two alleles form three genotypes, namely, DD, ID and II and the DD genotype has been linked to higher plasma ACE levels and cell ACE activity.^ In this study, the association between the ACE I/D polymorphism and carotid artery wall thickness measured by B-mode ultrasound was investigated in a biracial sample, and the association between the gene and incident CHD was investigated in whites and if the gene-CHD association in whites, if any, was due to the gene effect on atherosclerosis. The study participants are from the prospective Atherosclerosis Risk in Communities (ARIC) Study, including adults aged 45 to 65 years. The present dissertation used a matched case-control design for studying the associations of the ACE gene with carotid artery atherosclerosis and an unmatched case-control design for the association of the gene with CHD. A significant recessive effect of the D allele on carotid artery thickness was found in blacks (OR = 3.06, 95% C.I: 1.11-8.47, DD vs. ID and II) adjusting for age, gender, cigarette smoking, LDL-cholesterol and diabetes. No similar associations were found in whites. The ACE I/D polymorphism is significantly associated with coronary heart disease in whites, and while stratifying data by carotid artery wall thickness, the significant associations were only observed in thin-walled subgroups. Assuming a recessive effect of the D allele, odds ratio was 2.84 (95% C.I:1.17-6.90, DD vs. ID and II) and it was 2.30 (95% C.I:1.22-4.35, DD vs. ID vs. II) assuming a codominant effect of the D allele. No significant associations were observed while comparing thick-walled CHD cases with thin-walled controls. Following conclusions could be drawn: (1) The ACE I/D polymorphism is unlikely to confer appreciable increase in the risk of carotid atherosclerosis in US whites, but may increases the risk of carotid atherosclerosis in blacks. (2) ACE I/D polymorphism is a genetic risk factor for incident CHD in US whites and this effect is separate from the chronic process of atherosclerosis development. Finally, the associations observed here are not causal, since the I/D polymorphism is in an intron, where no ACE proteins are encoded. ^

Changes in blood lipids and their associations with changes in measures of height, weight and body mass index from age 8 to 18 years: Project Heartbeat!

A variety of studies indicate that the process of athrosclerosis begins in childhood. There was limited information on the association of the changes in anthropometric variables to blood lipids in school age children and adolescents. Previous longitudinal studies of children typically with insufficient frequency of observation could not provide sound inference on the dynamics of change in blood lipids. The aims of this analysis are (1) to document the sex- and ethnic-specific trajectory and velocity curves of blood lipids (TC, LDL-C, HDL-C and TG); (2) to evaluate the relationship of changes in anthropometric variables, such as height, weight and BMI, to blood lipids from age 8 to 18 years. ^ Project HeartBeat! is a longitudinal study designed to examine the patterns of serial change in major cardiovascular risk factors. Cohort of three different age levels, 8, 11 and 14 years at baseline, with a total of 678 participants were enrolled. Each member of these cohorts was examined three times per year for up to four years. ^ Sex- and ethnic-specific trajectory and velocity curves of blood lipids; demonstrated the complex and polyphasic changes in TC, LDL-C, HDL-C and TG longitudinally. The trajectory curves of TC, LDL-C and HDL-C with age showed curvilinear patterns of change. The velocity change in TC, HDL-C and LDL-C showed U-shaped curves for non-Blacks, and nearly linear lines in velocity of TG for both Blacks and non-Blacks. ^ The relationship of changes in anthropometric variables to blood lipids was evaulated by adding height, weight, or BMI and associated interaction terms separately to the basic age-sex models. Height or height gain had a significant negative association with changes in TC, LDL-C and HDL-C. Weight or BMI gain showed positive associations with TC, LDL-C and TC, and a negative relationship with HDL-C. ^ Dynamic changes of blood lipids in school age children and adolescents observed from this analysis suggested that using fixed screening criteria under the current NCEP guidelines for all ages 2–19 may not be appropriate for this age group. The association of increasing BMI or weight to an adverse blood lipid profile found in this analysis also indicated that weight or BMI monitoring could be a future intervention to be implemented in the pediatric population. ^

Functional and physical associations of beta1 integrins in the activation of human T lymphocytes

Adhesion involves interactions between cells or cells with extracellular matrix components and is a fundamental process for all multicellular organisms as well as many pathogenic microbes. Integrins are heterodimeric transmembrane proteins that function as adhesion molecules and transduce signals between the extracellular environment and the intracellular cytoskeletal machinery. β1 integrin subfamily is highly expressed on T lymphocytes and mediates cell spreading, adhesion and coactivation. T lymphocytes have an important role in the regulation and homeostasis of the immune system therefore, the goals of this study were to first to investigate β1 integrin interaction with fibronectin binding protein A (FnbpA), a surface protein expressed on gram-negative bacteria Staphylococcus aureus. Second, characterize the association and function of a non-integrin surface protein, CD98, with β1 integrins on T lymphocytes. ^ FnbpA binds to fibronectin (FN), also a ligand for α5β1 and α4β1 integrins on T lymphocytes. Since both bacterial proteins FnbpA and T cell integrins utilize FN, it was of interest to determine the effects FnbpA on T cell activation. Results demonstrated that recombinant FnbpA (rFnbpA) coimmobilized with OKT3 mediated T cell coactivation in a soluble FN-dependent manner. Integrin α5β1 was identified as the main integrin utilized by Staphylococcus aureus FnbpA from studies using soluble antibodies to inhibit T cell proliferation and parallel plate flow chamber assays. The mechanism of rFnbpA-mediated coactivation was one that used soluble FN as a bridge between rFnbpA and integrin α5β1 on the T lymphocyte. ^ Since integrins are utilized by T lymphocytes and bacterial proteins, it was of interest to identify proteins involved in integrin regulation. Anti-CD98 mAb 80A10 was identified and characterized from a screen to identify surface proteins involved in integrin signaling and functions. CD98 is a non-integrin protein that was sensitive to integrin inhibition in human T lymphocyte aggregation and activation, thus suggested that CD98 shared a common signaling pathway with integrins. These results led to the question of whether CD98 physically associates with β1 integrins. Fluorescence microscopy and biochemical analysis determined that CD98 is specifically associated with β1 integrin on human T lymphocytes and may be part of a larger multimolecular signaling complex. ^

Adherence to a lifestyle physical activity program: Trends over time and associations with processes of change and physical activity

Research on lifestyle physical activity interventions suggests that they help individuals meet the new recommendations for physical activity made by the Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM). The purpose of this research was to describe the rates of adherence to two lifestyle physical activity intervention arms and to examine the association between adherence and outcome variables, using data from Project PRIME, a lifestyle physical activity intervention based on the transtheoretical model and conducted by the Cooper Institute of Aerobics Research, Dallas, Texas. Participants were 250 sedentary healthy adults, aged 35 to 70 years, primarily non-Hispanic White, and in the contemplation and preparation stages of readiness to change. They were randomized to a group (PRIME G) or a mail- and telephone-delivered condition (PRIME C). Adherence measures included attending class (PRIME G), completing a monthly telephone call with a health educator (PRIME C), and completing homework assignments and self-monitoring minutes of moderate- to vigorous physical activity (both groups). In the first results paper, adherence over time and between conditions was examined: Attendance in group, completing the monthly telephone call, and homework completion decreased over time, and participants in PRIME G were more likely to complete homework than those in PRIME C. Paper 2 aimed to determine whether the adherence measures predicted achievement of the CDC/ACSM physical activity guideline. In separate models for the two conditions, a latent variable measuring adherence was found to predict achievement of the guideline. Paper 3 examined the association between adherence measures and the transtheoretical model's processes of change within each condition. For both, participants who completed at least two thirds of the homework assignments improved their use of the processes of change more than those who completed less than that amount. These results suggest that encouraging adherence to a lifestyle physical activity intervention, at least among already motivated volunteers, may increase the likelihood of beneficial changes in the outcomes. ^

Cross-cultural equivalence and associations among food insecurity and parental influences of children's fruit and vegetable consumption

Over the past several decades, the prevalence of obesity has dramatically increased. Cause for concern has increased because overweight and obesity are major contributors to morbidity and mortality. Intervention research aimed at reducing the prevalence of obesity has identified the family, specifically the parent, as a key component of the home environment. However, findings from dietary behavior change interventions have been disheartening because few studies have reported meaningful change, suggesting methodological and/or measurement issues within the intervention process. A lack of appropriate mediators and cross-cultural equivalence may partially explain the reason for little change.^ The study aims were to (1) evaluate the psychometric properties and assess the cross cultural equivalence of the Food Insecurity Scale (paper 1) and the modified Parent Feeding Practices Questionnaire (paper 2) and to assess the overall relationships among food insecurity, parent mediators, and parent behaviors towards children's dietary behavior (paper 3) through structural equation modeling and tests of invariance. The study aims were accomplished through conducting secondary analyses using baseline data from English- and Spanish-speaking Hispanic women who participated in the Healthy Families: Step by Step (BHF) study.^ Results indicated that although the FIS and the mPFPQ exhibited sound psychometric properties, the instruments exhibited a lack of invariance across language spoken groups. The lack of invariance was more pronounced in the FIS. Results also supported the theoretical framework identifying parent's perceived barriers and self-efficacy as mediators of parent's behaviors toward improving children's health eating. Results did not suggest that the relationships were moderated by food insecurity.^ In conclusion, the identification of differential item functioning in food insecurity and parent feeding practices may be beneficial in enhancing tailored interventions through the incorporation of cultural differences into the change mechanisms. However, future research needs to be conducted to determine if the lack of invariance demonstrates the existence of item bias or if it is a reflection of true difference among the language spoken groups. Additionally, obesity intervention studies targeting parent/family barriers and parent self-efficacy to provide/encourage healthy diets may result in an increase in parent behaviors which promote healthy eating behaviors among children. Future research should also examine a more complete causal pathway to determine whether parental changes in the mediators ultimately lead to an increase in healthy dietary behavior among children.^

Associations between vaccination and childhood cancers in Texas counties

Background. In Dr. Mel Greaves "delayed-infection hypothesis," postponed exposure to common infections increases the likelihood of childhood cancer. Hygienic advancements in developed countries have reduced children's exposure to pathogens and children encounter common infectious agents at an older age with an immune system unable to deal with the foreign antigens. Vaccinations may be considered to be simulated infections as they prompt an antigenic response by the immune system. Vaccinations may regulate the risk of childhood cancer by modulating the immune system. The aim of the study was to determine if children born in Texas counties with higher levels of vaccination coverage were at a reduced risk for childhood cancer.^ Methods. We conducted a case-control study to examine the risk of childhood cancers, specifically leukemia, brain tumors, and non-Hodgkin lymphoma, in relation to vaccination rates in Texas counties. We utilized a multilevel mixed-effects regression model of the individual data from the Texas Cancer Registry (TCR) with group-level exposure data (i.e., the county- and public health region-level vaccination rates).^ Results. Utilizing county-level vaccination rates and controlling for child's sex, birth year, ethnicity, birth weight, and mother's age at child's birth the hepatitis B vaccine revealed negative associations with developing all cancer types (OR = 0.81, 95% CI: 0.67–0.98) and acute lymphoblastic leukemia (ALL) (OR = 0.63, 95% CI: 0.46–0.88). The decreased risk for ALL was also evident for the inactivated polio vaccine (IPV) (OR = 0.67, 95% CI: 0.49–0.92) and 4-3-1-3-3 vaccination series (OR = 0.62, 95% CI: 0.44-0.87). Using public health region vaccine coverage levels, an inverse association between the Haemophilus influenzae type b (Hib) vaccine and ALL (OR: 0.58; 95% CI: 0.42–0.82) was present. Conversely, the measles, mumps, and rubella (MMR) vaccine resulted in a positive association with developing non-Hodgkin lymphoma (OR = 2.81, 95% CI: 1.27–6.22). ^

Determining associations and assessing methodological issues in a case-control study of hazardous air pollutants and neural tube defects

Recent studies have reported positive associations between maternal exposures to air pollutants and several adverse birth outcomes. However, there have been no assessments of the association between environmental hazardous air pollutants (HAPs) such as benzene, toluene, ethylbenzene, and xylene (BTEX) and neural tube defects (NTDs) a common and serious group of congenital malformations. Before examining this association, two important methodological questions must be addressed: (1) is maternal residential movement likely to result in exposure misclassification and (2) is it appropriate to lump defects of the neural tube, such as anencephaly and spina bifida, into a composite disease endpoint (i.e., NTDs). ^ Data from the National Birth Defects Prevention Study and Texas Birth Defects Registry were used to: (1) assess the extent to which change of residence may result in exposure misclassification when exposure is based on the address at delivery; (2) formally assess heterogeneity of the associations between known risk factors for NTDs, using polytomous logistic regression; and (3) conduct a case-control study assessing the association between ambient air levels of BTEX and the risk of NTDs among offspring. ^ Regarding maternal residential mobility, this study suggests address at delivery was not significantly different from using address at conception when assigning quartile of benzene exposure (OR 1.0, 95% CI 0.9, 1.3). On the question of effect heterogeneity among NTDs, the effect estimates for infant sex P = 0.017), maternal body mass index P = 0.016), and folate supplementation P = 0.050) were significantly different for anencephaly and spina bifida, suggesting it is often more appropriate to assess potential risk factors among subgroups of NTDs. For the main study question on the association between environmental HAPs and NTDs, mothers who have offspring with isolated spina bifida are 2.4 times likely to live in areas with the highest benzene levels (95% CI 1.1, 5.0). However, no other significant associations were observed.^ This project is the first to include not only an assessment of the relationship between environmental levels of BTEX and NTDs, but also two separate studies addressing important methodological issues associated with this question. Our results contribute to the growing body of evidence regarding air pollutant exposure and adverse birth outcomes. ^

Genome-wide algorithm for detecting CNV associations with diseases

SNP genotyping arrays have been developed to characterize single-nucleotide polymorphisms (SNPs) and DNA copy number variations (CNVs). The quality of the inferences about copy number can be affected by many factors including batch effects, DNA sample preparation, signal processing, and analytical approach. Nonparametric and model-based statistical algorithms have been developed to detect CNVs from SNP genotyping data. However, these algorithms lack specificity to detect small CNVs due to the high false positive rate when calling CNVs based on the intensity values. Association tests based on detected CNVs therefore lack power even if the CNVs affecting disease risk are common. In this research, by combining an existing Hidden Markov Model (HMM) and the logistic regression model, a new genome-wide logistic regression algorithm was developed to detect CNV associations with diseases. We showed that the new algorithm is more sensitive and can be more powerful in detecting CNV associations with diseases than an existing popular algorithm, especially when the CNV association signal is weak and a limited number of SNPs are located in the CNV.^

Micronutrient intakes and their associations with markers of inflammation, subclinical atherosclerosis, cardiovascular disease, type II diabetes and metabolic syndrome

We investigated cross-sectional associations between intakes of zinc, magnesium, heme- and non heme iron, beta-carotene, vitamin C and vitamin E and inflammation and subclinical atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). We also investigated prospective associations between those micronutrients and incident MetS, T2D and CVD. Participants between 45-84 years of age at baseline were followed between 2000 and 2007. Dietary intake was assessed at baseline using a 120-item food frequency questionnaire. Multivariable linear regression and Cox proportional hazard regression models were used to evaluate associations of interest. Dietary intakes of non-heme iron and Mg were inversely associated with tHcy concentrations (geometric means across quintiles: 9.11, 8.86, 8.74, 8.71, and 8.50 µmol/L for non-heme iron, and 9.20, 9.00, 8.65, 8.76, and 8.33 µmol/L for Mg; ptrends <0.001). Mg intake was inversely associated with high CC-IMT; odds ratio (95% CI) for extreme quintiles 0.76 (0.58, 1.01), ptrend: 0.002. Dietary Zn and heme-iron were positively associated with CRP (geometric means: 1.73, 1.75, 1.78, 1.88, and 1.96 mg/L for Zn and 1.72, 1.76, 1.83, 1.86, and 1.94 mg/L for heme-iron). In the prospective analysis, dietary vitamin E intake was inversely associated with incident MetS and with incident CVD (HR [CI] for extreme quintiles - MetS: 0.78 [0.62-0.97] ptrend=0.01; CVD: 0.69 [0.46-1.03]; ptrend =0.04). Intake of heme-iron from red meat and Zn from red meat, but not from other sources, were each positively associated with risk of CVD (HR [CI] - heme-iron from red meat: 1.65 [1.10-2.47] ptrend = 0.01; Zn from red meat: 1.51 [1.02 - 2.24] ptrend =0.01) and MetS (HR [CI] - heme-iron from red meat: 1.25 [0.99-1.56] ptrend =0.03; Zn from red meat: 1.29 [1.03-1.61]; ptrend = 0.04). All associations evaluated were similar across different strata of gender, race-ethnicity and alcohol intake. Most of the micronutrients investigated were not associated with the outcomes of interest in this multi-ethnic cohort. These observations do not provide consistent support for the hypothesized association of individual nutrients with inflammatory markers, MetS, T2D, or CVD. However, nutrients consumed in red meat, or consumption of red meat as a whole, may increase risk of MetS and CVD.^

Feeding practices and their associations with diarrhea incidence in a cohort of rural Egyptian infants

A study was conducted in 4 villages in Bilbeis, Egypt, to document the infant feeding practices and identify their determinants, and examine the associations between feeding practices and diarrhea incidence in infants. A cohort of 152 infants were followed from birth with twice-weekly home visits to record feeding practices and diarrheal illness. Cross-sectional information was obtained about child birth; early neonatal feeding practices; and the socioeconomic, demographic, and water and sanitation characteristics of study families.^ Prelacteal fees were given to 60% of the infants. Nineteen percent of the infants were wet nursed at least once during the first week of life. Breast-feeding prevalence declined from 100% among infants aged less than 12 weeks to 84% among those aged 44-47 weeks. The prevalence of exclusive breast-feeding among breast-fed infants was 38% in those aged less than 4 weeks, increased to 54% in age period 4-7 weeks, and then declined rapidly to 4% in age period 24-27 weeks. The patterns and determinants of consumption by breast-fed infants of specific supplements were examined in detail.^ Between birth and age 47 weeks, the diarrhea incidence rate per person-year among breast-fed infants (6.84 episodes) was identical to the rate among all infants (6.89 episodes). In age period 0-11 weeks, the diarrhea incidence rate among breast-fed infants receiving supplements was 1.3 times (95% confidence interval: 0.9-2.0) higher than the rate among those exclusively breast-fed. In other age periods, diarrhea incidence was generally nonsignificantly higher among exclusively breast-fed infants than among those partially breast-fed and those completely weaned.^ Both univariate and multivariate analyses were done to examine the associations between diarrhea incidence and the consumption by breast-fed infants of specific supplements. After multivariate adjustment, supplements that showed significant, borderline, or suggestive positive associations with diarrhea incidence were cereal-water, cheese, raw vegetables, and 'other' foods. Significant, borderline, or suggestive negative associations were observed between diarrhea incidence and the intake of fresh animal milk, and potatoes.^ To reduce the risk of diarrhea, indiscriminate use of supplements among Bilbeis infants aged less than 12 weeks should be strongly discouraged. While mothers in this area should be educated about methods of safer preparation, handling, storage, and administration of all weaning foods, their attention should be particularly drawn to the 4 foods that were found to be positively associated with diarrhea incidence among infants in this study. ^

Selection of body fat distribution indices in adults and associations with plasma lipid metabolism variables

Body fat distribution is a cardiovascular health risk factor in adults. Body fat distribution can be measured through various methods including anthropometry. It is not clear which anthropometric index is suitable for epidemiologic studies of fat distribution and cardiovascular disease. The purpose of the present study was to select a measure of body fat distribution from among a series of indices (those traditionally used in the literature and others constructed from the analysis) that is most highly correlated with lipid-related variables and is independent of overall fatness. Subjects were Mexican-American men and women (N = 1004) from a study of gallbladder disease in Starr County, Texas. Multivariate associations were sought between lipid profile measures (lipids, lipoproteins, and apolipoproteins) and two sets of anthropometric variables (4 circumferences and 6 skinfolds). This was done to assess the association between lipid-related measures and the two sets of anthropometric variables and guide the construction of indices.^ Two indices emerged from the analysis that seemed to be highly correlated with lipid profile measures independent of obesity. These indices are: 2*arm circumference-thigh skinfold in pre- and post-menopausal women and arm/thigh circumference ratio in men. Next, using the sum of all skinfolds to represent obesity and the selected body fat distribution indices, the following hypotheses were tested: (1) state of obesity and centrally/upper distributed body fat are equally predictive of lipids, lipoproteins and apolipoproteins, and (2) the correlation among the lipid-related measures is not altered by obesity and body fat distribution.^ With respect to the first hypothesis, the present study found that most lipids, lipoproteins and apolipoproteins were significantly associated with both overall fatness and anatomical location of body fat in both sex and menopausal groups. However, within men and post-menopausal women, certain lipid profile measures (triglyceride and HDLT among post-menopausal women and apos C-II, CIII, and E among men) had substantially higher correlation with body fat distribution as compared with overall fatness.^ With respect to the second hypothesis, both obesity and body fat distribution were found to alter the association among plasma lipid variables in men and women. There was a suggestion from the data that the pattern of correlations among men and post-menopausal women are more comparable. Among men correlations involving apo A-I, HDLT, and HDL$\sb2$ seemed greatly influenced by obesity, and A-II by fat distribution; among post-menopausal women correlations involving apos A-I and A-II were highly affected by the location of body fat.^ Thus, these data point out that not only can obesity and fat distribution affect levels of single measures, they also can markedly influence the pattern of relationship among measures. The fact that such changes are seen for both obesity and fat distribution is significant, since the indices employed were chosen because they were independent of one another. ^