Association of nitric oxide synthase gene polymorphisms (-786T>C, 4a4b, 894G>T) with primary ovarian insufficiency in Korean women

Objectives: The aim of our study was to investigate whether the endothelial nitric oxide synthase (eNOS) gene polymorphisms -786T>C, 4a4b, and 894G>T that affect nitric oxide (NO) generation confer a risk for primary ovarian insufficiency (POI) in Korean women. Study design: We genotyped 136 POI patients and 236 controls among Korean women for the three single nucleotide polymorphism sites with PCR-RFLP analysis. Differences in the eNOS -786T>C (rs2070744), 4a4b (rs61722009), and 894G>T (rs1799983) genotype frequencies between patients and controls were compared, and odds ratios and 95% confidence intervals were determined as a measure of the strength of the association between the genotypes and POI. Results: The POI patients had significantly decreased frequencies of the eNOS 894GT and -786TT/894GT genotypes (P = 0.025 and 0.027, respectively). However, the significant association between these eNOS polymorphisms and POI disappeared after adjustment for multiple comparisons (adjusted P = 0.075 and 0.081, respectively). The eNOS -786T/894G haplotype is more frequent in patients than controls (P = 0.030), whereas the -786T/894T haplotype was less frequent in patients (P = 0.031). The associations between -786/894 haplotypes and POI were confirmed by permutation tests. We did not find associations between the eNOS -786T>C or 4a4b polymorphisms and POI. Conclusions: Our data suggest that the eNOS -786T/894T haplotype is associated with a decreased POI risk, and we postulate that the eNOS -786T/894T haplotype may confer less risk on POI occurrence by reducing pathologically increased NO generation by eNOS in POI. Further study is warranted to elucidate the effect of the eNOS 894G>T polymorphism and POI occurrence. (c) 2012 Elsevier Ireland Ltd. All rights reserved.