EVIDENCE FOR A FAMILIAL PREGNANCY-INDUCED HYPERTENSION LOCUS IN THE ENOS-GENE REGION

Pregnancy-induced hypertension may be regarded as a manifestation of e ndothelial-cell dysfunction. The role of the eNOS gene in the developm ent of a familial pregnancy-induced hypertension was evaluated by anal ysis of linkage among affected sisters and in multiplex families (n = 50). Markers from a 4-cM region encoding the eNOS gene showed distorti on from the expected allele sharing among affected sisters (P = .001-. 05), and the statistic obtained from the multilocus application of the affected-pedigree-member method also showed distortion (T-[f(P=sqrt(P )]) = 3.53; P < .001). A LOD score of 3.36 was obtained for D7S505 whe n a best-fitting model derived from genetic epidemiological data was u sed, and LOD scores of 2.54-4.03 were obtained when various other gene tic models were used. Estimates of recombination rate, rather than max imum LOD-score values, were affected by changes in the genetic paramet ers. The transmission-disequilibrium test, a model-free estimate of li nkage, showed strongest association and linkage with a microsatellite within intron 13 of the eNOS gene (P = .005). These results support th e localization of a familial pregnancy-induced hypertension-susceptibi lity locus in the region of chromosome 7q36 encoding the eNOS gene.