1. Evidence for a familial pregnancy-induced hypertension locus in the eNOS-gene region.
- Author
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Arngrímsson R, Hayward C, Nadaud S, Baldursdóttir A, Walker JJ, Liston WA, Bjarnadóttir RI, Brock DJ, Geirsson RT, Connor JM, and Soubrier F
- Subjects
- Adult, Alleles, Endothelium, Vascular enzymology, Female, Genes, Genetic Linkage, Humans, Iceland epidemiology, Likelihood Functions, Lod Score, Matched-Pair Analysis, Microsatellite Repeats, Molecular Epidemiology, Pre-Eclampsia enzymology, Pre-Eclampsia epidemiology, Pregnancy, Pregnancy Complications, Cardiovascular enzymology, Pregnancy Complications, Cardiovascular epidemiology, Scotland epidemiology, Statistics, Nonparametric, Chromosomes, Human, Pair 7 genetics, Nitric Oxide Synthase genetics, Pre-Eclampsia genetics, Pregnancy Complications, Cardiovascular etiology
- 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 (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.
- Published
- 1997
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