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The APOA1/C3/A4/A5 cluster and markers of allostatic load in the Boston Puerto Rican Health Study.

ABSTRACT: The APOA1/C3/A4/A5 cluster encodes key regulators of plasma lipids. Interactions between dietary factors and single nucleotide polymorphisms (SNPs) in the cluster have been reported. Allostatic load, or physiological dysregulation in response to stress, has been implicated in shaping health disparities in ethnic groups. We aimed to determine the association between polymorphisms in the APOA1/C3/A4/A5 cluster with allostatic load parameters, alone, and in interaction with dietary fat intake in Puerto Ricans adults.Data on demographic and anthropometric measures, lifestyle behaviors, and medication use, as well as blood and urine samples for biomarker analysis, were obtained from participants of the Boston Puerto Rican Health Study (n=821, age 45-75 y). The 12 polymorphisms analyzed were not associated with allostatic load parameters. Significant interactions were observed between dietary fat intake and APOA1-75 in association with waist circumference (WC), (P=0.005), APOC3-640 with diastolic blood pressure (DBP), (P=0.003), and APOA4 N147S and APOA5 S19W with systolic blood pressure (SBP), (P=0.001 and P=0.002, respectively). Puerto Ricans homozygous for the common allele of APOA1-75, APOA4 N147S and APOA5 S19W had lower WC and SBP when consuming <31% of total fat from energy, than participants with the minor allele. Participants heterozygous for APOC3-640 had lower DBP at total fat intake ?31% from energy.SNPs in APOA1/C3/A4/A5, as modulated by dietary fat intake, appear to influence allostatic load parameters in Puerto Ricans.

SUBMITTER: Mattei J

PROVIDER: S-EPMC3004022 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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The APOA1/C3/A4/A5 cluster and markers of allostatic load in the Boston Puerto Rican Health Study.

Mattei J J Demissie S S Tucker K L KL Ordovas J M JM

Nutrition, metabolism, and cardiovascular diseases : NMCD 20100731 11

<h4>Background and aims</h4>The APOA1/C3/A4/A5 cluster encodes key regulators of plasma lipids. Interactions between dietary factors and single nucleotide polymorphisms (SNPs) in the cluster have been reported. Allostatic load, or physiological dysregulation in response to stress, has been implicated in shaping health disparities in ethnic groups. We aimed to determine the association between polymorphisms in the APOA1/C3/A4/A5 cluster with allostatic load parameters, alone, and in interaction w ...[more]

PMID: 20674306

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Project description:Puerto Ricans living in the United States mainland present multiple disparities in prevalence of chronic diseases, relative to other racial and ethnic groups. Allostatic load (AL), or the cumulative wear and tear of physiological responses to stressors such as major life events, social and environmental burden, has been proposed as a possible mechanism for the inequalities observed in minority groups, but has not been studied in Puerto Ricans. The aim of this study was to determine the association of AL to six chronic diseases (abdominal obesity, hypertension, diabetes, and self-reported cardiovascular disease (CVD), arthritis and cancer) in Puerto Ricans, and to contrast AL to metabolic syndrome (MetS). Participants of the Boston Puerto Rican Health Study (n=1116, ages 45-75 years) underwent a home-based interview, where questionnaires were completed and biological samples collected. A summary definition of AL was constructed using clinically-defined cutoffs and medication use for 10 physiological parameters in different body systems. Logistic regression models were run to determine associations between AL score and disease status, controlling for age, sex, smoking, alcohol use, physical activity, total fat intake and energy intake. Parallel models were also run with MetS score replacing AL. We found that increasing categories of AL score were significantly associated with abdominal obesity, hypertension, diabetes and self-reported cardiovascular disease (CVD) and arthritis, but not with self-reported cancer. The strength of associations of AL with all conditions, except diabetes and cancer, was similar to or larger than those of MetS score. In conclusion, Puerto Rican older adults experienced physiological dysregulation that was associated with increased odds of chronic conditions. AL was more strongly associated with most conditions, compared to MetS, suggesting that this cumulative measure may be a better predictor of disease. These results have prospective research implications for Puerto Ricans and other ethnic groups.

Project description:BACKGROUND: Central obesity is a rising epidemic, and often occurs in parallel with dyslipidemia. Furthermore, enhancement of ectopic fat deposition has been observed in both human studies and animal models of altered lipidemic control. Though APOA1/C3/A4/A5 genetic polymorphisms are associated with dyslipidemia, their effect on central obesity is less known. METHOD: The anthropometric and metabolic parameters were taken from obese (body mass index (BMI) ?25?kg?m(-2)) and non-obese healthy (BMI <25) Taiwanese patients at the initiation weight-loss intervention and 6 months later. The effects of APOA1/C3/A4/A5 genetic polymorphisms were analyzed cross-sectionally and longitudinally. Gender contributions were specifically examined. PATIENTS: Three hundred and ninety-eight participants (obese n=262; non-obese healthy n=136) were recruited in total, and 130 obese patients underwent weight-loss treatments. RESULTS: APOA5 rs662799 minor allele carriage was associated with unfavorable metabolic profiles in obese but not non-obese individuals at baseline. Further analysis identified gender-genotype interactions in waist-hip ratio (WHR), and that one rs662799 minor allele increased 0.032 WHR unit in obese males as analyzed by linear regression adjusted for age, BMI and plasma triglyceride (TG) (95% confidence interval (CI)=0.014-0.050, P=0.001). The rs662799-associated WHR elevation resulted in increased frequency of central obesity (WHR ?1.0) in rs662799 carrying obese males as analyzed by binary logistic regression adjusted for age, BMI and plasma TG (odds ratio=6.52, 95% CI=1.87-22.73, P=0.003). In contrast, APOA5 rs662799 and central obesity were no longer correlated 6 months into weight-loss treatments, owing to significant WHR reductions in male rs662799 minor allele carriers (P=0.001). Meanwhile, hypertriglyceridemia was more prevalent in both male and female obese rs662799 minor allele carriers at baseline (males, P=0.034, females, P=0.007). CONCLUSION: This study highlights the gender-specific and weight-sensitive effects of APOA5 rs662799 on central obesity in Taiwanese individuals, and that these effects are dyslipidemia-independent and weight-loss responsive.

Project description:BackgroundDyslipidemia contributes to the risk of many diseases, including stroke, cardiovascular disease and metabolic-related diseases. Previous studies have indicated that single nucleotide polymorphisms (SNPs) are associated with different levels of serum lipid. Therefore, this study explored the relationship between the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster gene polymorphisms and dyslipidemia in the total sample population and stratified by genders in a northeast Chinese population.MethodsA total of 3,850 participants from Jilin Province, China, were enrolled in our study, and their serum lipid levels were measured. Six functional SNPs (APOA1 rs5072, APOC3 rs5128, APOA4 rs5104, APOA5 rs651821, ZPR1 rs2075294 and BUD13 rs10488698) were genotyped using polymerase chain reaction and MALDI-TOF-MS. Logistic regression analysis was performed to explore the relationship of APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster gene polymorphisms with dyslipidemia. Linkage disequilibrium and haplotype analyses were performed with the SNPStats program and Haploview software.ResultsAll SNPs conformed to Hardy-Weinberg equilibrium. Logistic regression analysis revealed that rs5072, rs5128 and rs651821 were associated with hypertriglyceridemia, rs5104 and rs651821 were associated with low-HDL cholesterolemia in overall group. rs651821 was associated with hypertriglyceridemia and low-HDL cholesterolemia in both the male and female group. However, among females, rs5072 was observed to be associated with hypertriglyceridemia. Haplotype analysis showed that haplotypes TGCCGC and CAGCGC were associated with dyslipidemia in the overall, male and female groups.ConclusionSNPs in the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster were associated with dyslipidemia. Furthermore, the association of APOA1 rs5072 in this gene cluster with dyslipidemia differed between genders; thus, additional studies are needed to confirm this conclusion, and the mechanisms underlying these results warrant further exploration.

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The APOA1/C3/A4/A5 cluster and markers of allostatic load in the Boston Puerto Rican Health Study.

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The APOA1/C3/A4/A5 cluster and markers of allostatic load in the Boston Puerto Rican Health Study.

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