[Association of genetic polymorphisms in endothelial nitric oxide synthase 3 gene with recurrent early spontaneous abortion].
ABSTRACT To explore the association of nitric oxide synthase 3 (NOS3) gene variable number of tandem repeat(VNTR) polymorphism in intron 4 and an 894(G/T) mutation at exon 7 with recurrent early spontaneous abortion (RESA).
One hundred and forty RESA women (patient group) and 140 healthy women with at least 1 pregnancy and without a history of pregnancy complications (control group) were included. The genotypes of NOS3 gene VNTR polymorphism were determined by polymerase chain reaction and agarose gel electrophoresis. The 894(G/T) mutation of genotypes of NOS3 gene at exon 7 was assessed by polymerase chain reaction-restrictive fragment length polymorphism.
The frequencies of aa and ba genotypes and a allele of NOS3 gene were higher in patient group than in control group (chi square: 4.51, P< 0.05; chi square: 4.29, P<0.05). The aa and ba genotypes were significantly associated with RESA (OR:1.8, 95% CI: 1.04-3.24). There was no significant difference in TT and GT genotypes and T allele of NOS3 gene between RESA patient group and control group (chi square: 1.16, P> 0.05; chi square:1.12, P> 0.05). 894(G/T) polymorphism may be not associated with RESA.
The genetic polymorphism of NOS3 gene 27 bp VNTR was associated with RESA. The genetic polymorphism of NOS3 gene 894(G/T) may be not associated with RESA. These results support that a allele of the NOS3 gene may be susceptibility allele.
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ABSTRACT: 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.Human Fertility 09/2013; 16(3):200-6. · 1.02 Impact Factor
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ABSTRACT: Recurrent pregnancy loss, defined as a pregnancy failure occurring before 24 weeks of gestation more than two or three times according to most definitions, is a fertility defect encountered in 1-5% of the patients. This defect is of course of multifactorial origin. Among the possible origins of recurrent pregnancy loss are uterine structural defaults, defective ploidy control of the embryo, defective immunological dialog between the embryo (or the fetus) and the uterus sometimes in relation with immunological disorders (such as autoimmune diseases), thrombophilia, and free radical metabolism imbalance. Numerous studies attempted to correlate variants of genes supposed to be intervening in the different facets of the early maternal-fetal or maternal-embryonic dialog, and eventually modify the outcome of fertilization, leading to success or failure of post-implantation development. The objective of the present review is to portray the major genes and gene polymorphisms studied for their putative association with recurrent pregnancy loss. Most of these genes have been studied as candidate genes for which strong biological arguments were put forward as to their putative involvement in recurrent pregnancy loss. They were mostly studied by genetic analysis, often in various populations of different ethnic origins, throughout the world. Some of these studies were available only in English as abstracts and were nevertheless used if the information was given with enough detail. With the space being too short to depict all the available literature, different major pathways releva nt to the scientific question are presented without any attempt to hide the fact that discordant views often aroused for a given gene.Biomedical journal. 09/2014;
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ABSTRACT: Recurrent pregnancy loss (RPL) is a multifactorial disorder, both genetic and environmental factors contribute to the development of RPL. Recently, the association between endothelial nitric oxide synthase (eNOS) gene polymorphisms and unexplained recurrent pregnancy loss (URPL) has been reported, and the results were inconsistent. Hence, we performed the meta-analysis to drive a more precise estimation of association between eNOS polymorphisms and URPL. Odds ratio (OR) and its 95 % confidence interval were calculated under co-dominant (AA vs. BB, TT vs. GG) and additive (A vs. B, T vs. G) genetic models. Studies of eNOS intron 4 VNTR and Glu298Asp were separated by ethnicities. 13 studies included 1,769 URPL cases and 1,376 healthy controls on eNOS intron 4 VNTR polymorphism, and 11 studies were involved in Glu298Asp polymorphism with 1,498 URPL cases and 1,123 healthy controls. The integrated results showed that eNOS Glu298Asp polymorphism was associated with URPL [ORs were 1.91 (1.42-2.56), P < 0.001; 1.67 (1.36-2.04), P < 0.001, respectively]. When analyses were separated by ethnic subgroups, the association between eNOS Glu298Asp polymorphism and URPL was only observed in East Asians [OR = 1.88 (1.52-2.33), P < 0.001 under additive model], and there was no association between eNOS intron 4 VNTR polymorphism and URPL in Caucasians and East Asians. The results indicated a significant association between eNOS Glu298Asp polymorphism and URPL in East Asians. No association was observed between eNOS intron 4 VNTR polymorphism and URPL in Caucasians and East Asians.Molecular Biology Reports 02/2014; · 1.96 Impact Factor