Evidence for a Familial Pregnancy-Induced Hypertension Locus in the eNOS-Gene Region

Pregnancy-induced hypertension may be regarded as a manifestation of endothelial-cell dysfunction. The role of the eNOS gene in the development of a familial pregnancy-induced hypertension was evaluated by analysis of linkage among affected sisters and in multiplex families ( n = 50). Markers from a 4-cM region encoding the eNOS gene showed distortion 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 when a best-fitting model derived from genetic epidemiological data was used, and LOD scores of 2.54–4.03 were obtained when various other genetic models were used. Estimates of recombination rate, rather than maximum LOD-score values, were affected by changes in the genetic parameters. The transmission-disequilibrium test, a model-free estimate of linkage, showed strongest association and linkage with a microsatellite within intron 13 of the eNOS gene ( P = .005). These results support the localization of a familial pregnancy-induced hypertension—susceptibility locus in the region of chromosome 7q36 encoding the eNOS gene.