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

item MATTEI, JOSIEMER - Harvard University
item DEMISSIE, SERKALEM - Boston University
item TUCKER, KATERINE - Northeastern University
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Nutrition Metabolism and Cardiovascular Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/15/2010
Publication Date: 11/1/2011
Citation: Mattei, J., Demissie, S., Tucker, K.L., Ordovas, J.M. 2011. The APOA1/C3/A4/A5 cluster and markers of allostatic load in the Boston Puerto Rican Health Study. Nutrition Metabolism and Cardiovascular Disease. 21(11):862-870.

Interpretive Summary: Common chronic diseases of aging disproportionately affect minorities in the US, including Puerto Ricans living on the US mainland. Many social, economic, genetic and other biological factors may contribute to these health disparities. The biological factors may include an individual’s overall physiological response to stress, a concept referred to as ‘allostatic load’. Allostatic load encompasses a set of factors that reflect disturbances in the body’s physiology as indicated by blood pressure, waist circumference, stress hormones, fats in the blood (lipids), and others. In the current study, we investigated relationships between allostatic load and a specific set of genetic factors. The genetic factors, referred to as the APOA1/C3/A4/A5 cluster, include five genes that are involved in the regulation of blood lipids such as triglycerides and high density lipoprotein cholesterol. We did not observe direct links between the genetic factors of the cluster and the components of allostatic load. However, when we analyzed relationships between the amount of fat in the diet and the genetic variants in the cluster, we observed relationships between particular genetic factors and two allostatic load components, waist circumference and blood pressure. We refer to the results we detected as a ‘gene-diet interaction’, in which outcomes affecting health are observed only under certain dietary conditions. Incomplete understanding of the factors contributing to health disparities, particularly in Puerto Ricans, has limited achievement of the NIH goal of eliminating health disparities. This study illustrates the complexity of relationships across genetic and environmental, and suggests new ways in which health outcomes may be improved in this population.

Technical 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 less than 31% of total fat from energy, than participants with the minor allele. Participants heterozygous for APOC3-640 had lower DBP at total fat intake greater than or equal 31% from energy. SNPs in APOA1/C3/A4/A5, as modulated by dietary fat intake, appear to influence allostatic load parameters in Puerto Ricans.