Recurrent early pregnancy loss and endothelial nitric oxide synthase gene polymorphisms.
OBJECTIVE
Studies on the relation between endothelial nitric oxide synthase (eNOS) activity in implantation and maintenance of pregnancy highlights the importance of eNOS gene polymorphisms in recurrent early pregnancy loss (REPL). We investigated the relationship between idiopathic REPL and polymorphisms in eNOS among South Indian women.


METHODS
A case-control study comprising 145 females with REPL and 99 control females. The polymorphisms studied include a 27 bp intron 4 repeat, Glu298Asp variation of exon 7 and a novel 140 A --> G polymorphism in intron 6. A polymerase chain reaction-based di-deoxy dye terminator sequencing method was used for genotyping.


RESULTS
A novel A --> G polymorphism was identified in intron 6. The more frequent b allele of intron 4 repeat was present at a frequency of 0.84 in cases as compared to 0.86 in controls (O.R 1.17); the G allele of exon 7 coding for the wild-type glutamate containing isoform was present at a frequency of 0.79 in cases and 0.83 in controls (O.R 1.30, CI 0.6-2.8). The intron 6 variant A allele was present at a frequency of 0.58 in cases and 0.45 in controls (O.R 0.59, CI 0.33-1.08). Overall, the polymorphism in intron 6, in homozygous condition, exhibited a significant association to the risk of REPL (O.R 0.43, CI 0.21-0.89), P: 0.021).


CONCLUSIONS
The present study identifies and validates a novel polymorphism in the eNOS gene which was found associated with the risk of REPL.
Suryanarayana
Venkata
V
Centre for Cellular and Molecular Biology, Uppal Road, 500 007 Hyderabad, Andhra Pradesh, India.
Rao
Lakshmi
L
Kanakavalli
Murthy
M
Padmalatha
Venkata
V
Deenadayal
Mamata
M
Singh
Lalji
L
D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007194:India; D007438:Introns; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011247:Pregnancy
D052250:Nitric Oxide Synthase Type III