Evidence for a familial pregnancy-induced hypertension locus in the eNOS-gene region. |
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Authors: | R Arngrímsson C Hayward S Nadaud A Baldursdttir J J Walker W A Liston R I Bjarnadttir D J Brock R T Geirsson J M Connor and F Soubrier |
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Institution: | R Arngrímsson, C Hayward, S Nadaud, A Baldursdóttir, J J Walker, W A Liston, R I Bjarnadóttir, D J Brock, R T Geirsson, J M Connor, and F Soubrier |
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Abstract: | 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 (Tf(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. |
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