Genetic and dietary determinants of allostatic load and chronic disease in the Boston Puerto Rican health study

Background. Puerto Ricans living in the US have a high prevalence of multiple chronic conditions including diabetes, hypertension and obesity. As nearly four million Puerto Ricans live in the US, responding to the health issues of this ethnic group is imperative. Allostatic load (AL) is being explored as a possible mechanism for the health disparities observed in minority groups. AL refers to the cumulative dysregulation of physiological parameters in response to stressors, and has been associated with increased morbidity and mortality risk. Individual genetic variations and behavioral responses, such as diet, may also alter the way a person responds physiologically to stress. Variations in minor allele frequencies (MAF) and in population differentiation (FST) in populations contribute to group differences in some common complex diseases, and can indicate local adaptation to environmental pressures. Genetic variability in the form of single nucleotide polymorphisms (SNPs) may partly explain the response to diet in the manifestation of AL and disease. Genetic and AL research in Puerto Ricans are limited.;Objective. To determine the genetic and dietary factors that contribute to AL and chronic disease in Puerto Ricans by: (1) computing MAF and FST for 101 SNPs in 30 genes of lipid and glucose metabolism and inflammation response, in comparison with non-Hispanic whites (NHW), (2) determining the association between SNPs in selected gene loci, alone, and in interaction with dietary fat intake, with physiological parameters of AL, and (3) estimating the associations of AL with chronic disease in Puerto Ricans.;Methods. Analysis was conducted with data from questionnaires and biological samples collected from participants of the Boston-Puerto Rican Heath Study (n=1360, ages 45 to 75 y). MAF and FST measures were calculated to prioritize selection of SNPs for association analysis. SNPs in the APOA1/C3/A4/A5 cluster were analyzed, alone, and in interaction with total dietary fat, for association with 10 parameters of AL. Logistic regressions were run to determine association of AL categories with chronic diseases.;Results. Puerto Ricans had significantly different MAF distribution in 46% of SNPs than similarly aged NHW. They had lower frequency of protective alleles and greater prevalence of risk alleles for disease-associated SNPs. Puerto Ricans showed exceptional FST values in SNPs from chromosome 11, and in intronic, non-synonymous and promoter SNPs. Twelve SNPs analyzed in the APOA1/C3/A4/A5 cluster were not associated with AL parameters, but interactions with dietary fat intake were observed. Puerto Ricans carrying the common allele of APOA1-75, APOA4 N147S or APOA5 S19W had lower waist circumference and blood pressure only when consuming less than 31% of total fat from energy. At this intake level, elevated plasma triglycerides and total cholesterol was observed for subjects with APOA5 -1131T>C common allele. Increasing categories of AL were significantly associated with abdominal obesity, hypertension, diabetes and self-reported CVD and arthritis, but not with self-reported cancer.;Conclusions. Puerto Rican older adults living in Boston present high prevalence of several chronic conditions. Their unique genetic profile, in interaction with total dietary fat intake, modulates physiological parameters of AL in a way that may partly explain health disparities in this group. Puerto Ricans experience AL that is associated with increased odds of some chronic conditions. The results of this dissertation suggest prospective implications in public health and research, such as an approach for selection of candidate genes for association studies, a novel AL definition, and targeted dietary interventions for Puerto Ricans.