Combinations of Variations in Multiple Genes Are Associated With Hypertension

作者：Scott M. Williams, Jonathan H. Addy, John A. Phillips, Min Dai, John Kpodonu, James Afful, Harold Jackson, K.-K.Li Joseph, Felicia Eason, Mark M Murray, Pamela Epperson, Adwoa Aduonum, Lee-Jun Wong, Pedro A. José, Robin Allen Felder · 发表于：Hypertension · 年份：2000 · DOI：10.1161/01.hyp.36.1.2 · 被引用次数：145 · 研究领域：Renin-Angiotensin System Studies、Genetic Associations and Epidemiology、Hormonal Regulation and 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 populations. Some of the confusion from previous studies is probably due to undetected gene-gene interactions. Instead of focusing on the effects of single genes on hypertension, we examined the effects of interactions of alleles at 4 candidate loci. Three of the loci are in the renin-angiotensin-system, angiotensinogen, ACE, and angiotensin II type 1 receptor, and they have been associated with hypertension in at least 1 previous study. The fourth locus studied 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 to either allele or genotype frequencies. However, when we tested for nonallelic associations (linkage disequilibrium), we found that of the 120 multilocus 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 rather than variants of a single gene underlie the genetic basis of hypertension in our study subjects. We hypothesize that such interactions may account...