Endothelial nitric oxide synthase gene variants and haplotypes associated with an increased risk of idiopathic recurrent miscarriage

Abstract

We investigated the association of endothelial nitric oxide synthase (NOS3) polymorphisms rs2070744 (-786T> C), 27-bp repeat 4b/4a, rs1799983 (Glu298Asp), rs3918188 (-734C> A), and rs743507 (113G> A) with idiopathic recurrent miscarriage (IRM). This was a case-control study involving women with confirmed IRM (n = 296), and 305 age- and ethnically matched control women. NOS3 rs2070744, rs1799983, rs3918188, and rs743507 genotyping was done by TaqMan assays; NOS3 4b/4a genotyping was done by PCR-ASA. A higher frequency of -786C and 298Asp alleles was seen in IRM cases, which remained associated independently with IRM on multivariate analysis. Allele and genotype distribution of 4b/4a, rs3918188 (-734C> A) and rs743507 (113A> G) were comparable between IRM cases and control women. Taking homozygous wild-type genotype as a reference, regression analysis confirmed the association of Glu298Asp and -786T/C, and rs743507 homozygous carriers with IRM risk. Marked linkage disequilibrium was seen between tested NOS3 variants, thus allowing the construction of 5-locus [-786T> C/4b4a/Glu298Asp/-734C> A/113G> A] haplotypes. Taking the common T4bGCA haplotype as a reference, multivariate analysis confirmed the positive association of C4bTCG haplotype with IRM, after controlling for traditional covariates. Genetic variation at the NOS3 locus represents a genetic risk factor for increased susceptibility to IRM.

Influence of MBL2 and NOS3 polymorphisms on spontaneous preterm birth in North East Brazil: genetics and preterm birth

“…Our results agree with Luo et al [29], Parveen et al [31] and Almawi et al [32], that revealed a significant association between the rs1799983 genotype distribution in recurrent miscarriage patients. In these studies, women with recurrent spontaneous abortion had a significantly higher frequency of G/T genotype and lower frequency of the G allele compared to control women.…”

The prevalence of combined vascular endothelial growth factor, endothelial nitric oxide synthase and thrombin‐activatable fibrinolysis inhibitor genetic polymorphisms among Egyptian patients with recurrent spontaneous abortion

“…After publishing our previous results which concluded that; TAFI 1040C/T could not be considered as a molecular predictive factor for RSA in Egyptians, we could not find any published research that investigated the role of TAFI whether on the molecular or antigen level in pregnancy nor RSA until the time of preparation of the current work. Both eNOS T‐786C and 27bp VNTR of intron 4 were associated in 10 patients who were negative for other studied genes, similarly Almawi et al , found genetic association study replicated a significant association for eNOS variants and haplotypes with RSA. While Shin et al , could not find such an association among Korean patients.…”

Investigation of the association between eNOS gene promoter polymorphism (-786 T>C) and idiopathic recurrent pregnancy loss in Iranian women

“…Another study on Lebanon women suggested that eNOS gene promoter variation (-786T > C) sustained a substantial impact on RPL in their women population. [26]. An investigation on a group of Egyptian women exposed a signi cantly association between RPL and this variant [27].…”