The eNOS gene: a candidate for the preeclampsia susceptibility locus?
OBJECTIVE
To investigate the endothelial cell nitric oxide synthase (eNOS) gene as a candidate for susceptibility to preeclampsia.


METHODS
Twenty-six Australian families containing 11 eclamptics, 59 severe preeclamptics, and 27 mild preeclamptics were used to test for linkage between the eNOS gene region and preeclampsia. Two microsatellite markers (D7S483 and D7S505) in the proximity of the eNOS gene were used.


METHODS
Logarithm of odds (LOD) scores were used to examine the cosegregation of alleles with the disease under a variety of inheritance models. Model-independent analysis, affected pedigree member method (AFFPED), and pairwise haplotype sharing between affected sibs were also used.


RESULTS
Two-point LOD score analysis gave no evidence of linkage between preeclampsia and two markers in close proximity to the eNOS gene (LOD scores < 1) for any of the inheritance models investigated, with no evidence of heterogeneity between pedigrees. The AFFPED and the pairwise haplotype sharing test on affected sibs also gave no evidence of linkage (p-values > 0.05).


CONCLUSIONS
This study provides no evidence for linkage between two markers in close proximity to the eNOS gene and preeclampsia in these families. These results do not support the recent suggestion that eNOS could be a familial pregnancy-induced hypertension gene (Arngrimsson R, et al., Am J Hum Genet 1997;61:354-62). Distinguishing preeclampsia from other hypertensive disorders in pregnancy is difficult. Hypertension appears to be a consequence, rather than a primary cause of preeclampsia. Given the vasodilatory role of the eNOS gene product, it is possible that the linkage recently reported for eNOS reflects its relationship with hypertension rather than preeclampsia.
Lade
J A
JA
Department of Perinatal Medicine, Royal Women's Hospital, Carlton, Victoria, Australia. jlade@ariel.ucs.unimelb.edu.au
Moses
E K
EK
Guo
G
G
Wilton
A N
AN
Grehan
M
M
Cooper
D W
DW
Brennecke
S P
SP
D001315:Australia; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy
D005819:Genetic Markers; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III