Evaluation of How Gene-Job Strain Interaction Affects Blood Pressure in the PAMELA Study

Abstract

To see whether there is interaction between single nucleotide polymorphisms (SNPs) belonging to candidate genes for hypertension and job strain and its components (job demand and job control) in an accurately phenotyped Italian cohort (Pressioni Arteriose Monitorate E Loro Associazioni). From the Pressioni Arteriose Monitorate E Loro Associazioni cohort, we sampled 924 employed men and women who had completed a modified version of the Karasek questionnaire and for whom deoxyribonucleic acid information was available. We selected 1,510 common tagging and putative functional SNPs in 92 candidate autosomal genes involved in sympathetic nervous system, oxidative stress, renin-angiotensin-aldosterone system, and sodium balance. The interaction of each candidate SNP with the perceived job stress scores on ambulatory systolic and diastolic blood pressures was evaluated by adding product terms to a multiple regression linear model, adjusted for sex, age, total cholesterol, and body mass index. Among all the SNPs tested, the interaction of SNP rs11210278 located on the endothelin 2 gene and job control was statistically significant after controlling for multiple testing, using false discovery rate (unadjusted p = .00000661; p adjusted for false discovery rate = .0085), indicating an inverse association with systolic blood pressure for the homozygous wild-type allele (C/C) and a positive association for the variant genotypes (C/T and T/T). We show that the hypertensive response to job strain is present only in carriers of the rs11210278 wild-type genotype. The phenomenon is discussed in relationship to the controversial results of field studies on job strain and hypertension.