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.
Arngrímsson
R
R
Institute of Medical Genetics, Glasgow University. reynira@rsp.is
Hayward
C
C
Nadaud
S
S
Baldursdóttir
A
A
Walker
J J
JJ
Liston
W A
WA
Bjarnadóttir
R I
RI
Brock
D J
DJ
Geirsson
R T
RT
Connor
J M
JM
Soubrier
F
F
D000328:Adult; D000483:Alleles; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D005796:Genes; D008040:Genetic Linkage; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D016013:Likelihood Functions; D008126:Lod Score; D016555:Matched-Pair Analysis; D018895:Microsatellite Repeats; D017720:Molecular Epidemiology; D019001:Nitric Oxide Synthase / Q000235:genetics*; D011225:Pre-Eclampsia / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000201:enzymology / Q000453:epidemiology / Q000209:etiology*; D012606:Scotland / Q000453:epidemiology; D018709:Statistics, Nonparametric
D019001:Nitric Oxide Synthase