Evidence for a familial pregnancy-induced hypertension locus in the eNOS-gene region

Am J Hum Genet. 1997 Aug;61(2):354-62. doi: 10.1086/514843.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Chromosomes, Human, Pair 7 / genetics*
  • Endothelium, Vascular / enzymology
  • Female
  • Genes
  • Genetic Linkage
  • Humans
  • Iceland / epidemiology
  • Likelihood Functions
  • Lod Score
  • Matched-Pair Analysis
  • Microsatellite Repeats
  • Molecular Epidemiology
  • Nitric Oxide Synthase / genetics*
  • Pre-Eclampsia / enzymology
  • Pre-Eclampsia / epidemiology
  • Pre-Eclampsia / genetics*
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / enzymology
  • Pregnancy Complications, Cardiovascular / epidemiology
  • Pregnancy Complications, Cardiovascular / etiology*
  • Scotland / epidemiology
  • Statistics, Nonparametric


  • Nitric Oxide Synthase