Combinations of variations in multiple genes are associated with hypertension

The genetic analysis of hypertension has revealed complex and inconsistent results, making it difficult to draw clear conclusions regarding the impact of specific genes on blood pressure regulation in diverse human population s. Some of the confusion from previous studies is probably due to undetecte d gene-gene interactions. Instead of focusing on the effects of single gene s on hypertension, we examined the effects of interactions of alleles at 4 candidate loci. Three of the loci are in the renin-angiotensin-system, angi otensinogen, ACE, and angiotensin II type I receptor, and they have been as sociated with hypertension in at least 1 previous study, The fourth locus s tudied is a previously undescribed locus, named FJ. In total, 7 polymorphic sites at these loci were analyzed for their association with hypertension in 51 normotensive and 126 hypertensive age-matched individuals. There were no significant differences between the 2 phenotypic classes with respect t o either allele or genotype frequencies. However, when we tested for nonall elic associations (linkage disequilibrium), we found that of the 120 multil ocus comparisons, 16 deviated significantly from random in the hypertensive class, but there were no significant deviations in the normotensive group. These findings suggest that genetic interactions between multiple loci rat her than variants of a single gene underlie the genetic basis of hypertensi on in our study subjects. We hypothesize that such interactions may account for the inconsistent findings in previous studies because, unlike our stud y, prior studies almost always examined single-locus effects and did not co nsider the effects of variation at other potentially interacting loci.