Hypertension is a common disease, affecting over 78 million adults in the US every year (Go et al., 2014). African Americans are disproportionately affected by this disease, with an earlier age of onset as well as higher rates of complications than adults of other racial/ethnic backgrounds (Nwankwo, Yoon, Burt, & Gu, 2013). The etiology of hypertension is complex and multifactorial. Studies have identified social, biological, environmental, and genetic risk factors for hypertension, but few studies have considered the ways in which these risk factors interact or work together in elevating risk among African Americans. Social factors such as experiences of discrimination related to skin color have been associated with high blood pressure in diverse populations, especially in low-income groups (Gravlee & Dressler, 2005; Sweet, McDade, Kiefe, & Liu, 2007). Further, although self-reported race has been associated with poor mental and physical health outcomes in African Americans (Monk, 2015), little is known about the gene-environment interaction that may exacerbate poor outcomes.
Both GWAS and candidate gene analyses were utilized to study the relationship between everyday (ED) and major life discrimination (MLD) with increases in systolic (SBP) and diastolic (DBP) blood pressure among African Americans in the Jackson Heart Study. Known predictors of blood pressure, such as age, sex, BMI, antihypertensive use and smoking status, were assessed in a multiple regression model including all predictors. Using multiple linear regression models, we assessed the associations between each predictor discrimination variable including and outcome variables (i.e., SBP and DBP) adjusted for age, sex, BMI, antihypertensive use and current smoking status. We used multiple linear regression models to test for association between each SNP and the blood pressure phenotypes (i.e., SBP and DBP). Each SNP was tested for additive effects in association with the outcome of interest in a test with one degree of freedom. We also tested the SNP ´ perceived discrimination interaction effects of SBP and DBP using multivariable linear mixed models with age, sex, BMI, antihypertensive medication use and top 10 Principal Components of the GWAS data as covariates.
A total of 2,937 participants had both phenotypic and genetic data and were included in analyses for this study. This sample had a mean age of 55 years old, and the majority of the sample were female, obese, non-smokers, had hypertension, and were on antihypertension medication. Mean SBP and DBP were 126.8 and 79.1 mmHg, respectively. Overall, discrimination reported among participants in our sample was low. Multiple linear regression indicates no association between discrimination and blood pressure after adjusting for age, gender, BMI, antihypertensive medication use and current smoking status. Subsequent candidate gene analysis identified five SNPs (rs7602215, rs3771724, rs1006502, rs1791926, and rs2258119) that interacted with discrimination and SBP, and three SNPs (rs2034454, rs7602215, and rs3771724) that interacted with discrimination and DBP. Most notably, there was a significant SNP x discrimination interaction for two SNPs on the SLC4A5 gene: rs3771724 (MLD: SBP p=.034, DBP p=.031; ED: DBP: p=.016) and rs1006502 (MLD: SBP p=.034, DBP p=.030; ED: DBP p=.015).
Our data add to the evidence supporting an association between SNPs in the SLC4A5 gene and increases in blood pressure is one of a number of sample populations of AA reporting similar results, thus showing the replicability of the SLC4A5 gene across various samples (Barkley et al., 2004; Taylor et al., 2012; Taylor, Sampson, Taylor, Caldwell, & Sun, 2013). Replication with similar epidemiological samples is required to determine the role of genes and psychological stressors in the development and expression of hypertension among this understudied population.