Abstract-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 for the inconsistent findings in previous studies because, unlike our study, prior studies almost always examined single-locus effects and did not consider the effects of variation at other potentially interacting loci. (Hypertension. 2000;36:2-6.)

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1 ) The antifertility effects of a number of simple alkane sulphonic esters have been examined in the male rat by a combination of serial mating of treated animals and histological examination of the testes. The results are compared and contrasted with those obtained with Busulphan (Myleran), dimethylmyleran and various derivatives of ethyleneimine.(2) A spectrum of results on various stages of spermatogenesis has been obtained, which is difficult to reconcile with a common mode of action due to alkylation of cellular materials.(3) Certain simple esters produce strikingly different effects. Thus, methylethanesulphonate and methylmethanesulphonate cause early sterility due to interference with spermatids and spermatozoa. Isopropyl alkane sulphonates, on the other hand, cause sterility only after a delay of several weeks.(4) These esters are effective by mouth and their action is cumulative. Methylmethanesulphonate and methylethanesulphonate in small daily doses produce predictable periods of sterility, according to the dose rate given, which are completely reversible. There is no indication of any action on libido, nor evidence so far of toxic effects from these courses of treatment.(5) With the series of compounds examined, it has been possible to move the focus of drug action from spermatogonia to spermatids and spermatozoa with reduction of side effects. It is concluded that this work demonstrates that selective interference with fertility in the male is a distinct possibility.