Polymorphisms in the endothelial nitric oxide synthase gene associated with recurrent miscarriage

Abstract

ABSTRACT. Endothelial nitric oxide synthase (eNOS) is an enzyme that influences placental human chorionic gonadotropin production during gestation. Previous studies have indicated an association between eNOS activity, implantation, and maintenance of pregnancy, but proposed associations between polymorphisms of the eNOS gene and recurrent miscarriage (RM) are controversial. To identify markers contributing to the genetic susceptibility to RM, we examined the potential association between RM and 8 single nucleotide polymorphisms (SNPs; rs1799983, rs2070744, rs11771443, rs3918188, rs2853796, rs7830, rs1541861, and rs2853792) of the eNOS gene using the MassARRAY system (Sequenom, USA). The enrolled participants included 192 RM patients and 201 women with normal fertility as controls. The results showed that rs1799983 at exon 7 of the eNOS gene was significantly associated with RM (genotype: chi-square = 15.071, P = 0.001; allele: chi-square = 6.250, P = 0.016). Another significant association was observed for rs11771443 in the promoter (genotype: chi-square = 6.259, P = 0.044; allele: chi-square = 7.076, P = 0.008). Furthermore, strong linkage disequilibrium was observed in 3 blocks (Dꞌ > 0.9), and significantly fewer T-T-G haplotypes (chi-square = 5.981, P = 0.015) residing in block 1 were found in RM patients. These findings point to a role for eNOS gene polymorphisms in RM in the Chinese Han population and may be informative for future genetic or neurobiological studies of RM.

The interaction effect of angiogenesis and endothelial dysfunction-related gene variants increases the susceptibility of recurrent pregnancy loss

“…Several meta-analyses revealed a close relationship between the G894T variant of the NOS3 gene and idiopathic RPL [10,17,18]. In the Chinese, there was a significant reduction in the 894G allele frequency in patients with RPL [41], corresponding to data obtained in Indian populations [38], Koreans [42], and the present study. Additionally, Shin et al found that the 894TT genotype of the NOS3 gene was significantly more common in the RPL group than in the control group (OR = 2.39; CI 1.25-4.58; p = 0.008) [42].…”

Molecular Analysis of rs2070744 and rs1799983 Polymorphisms of NOS3 Gene in Iranian Patients With Multiple Sclerosis

“…Several reports have been showed that c.-813C>T (rs2070744) polymorphism in the 5′ flanking (promoter) region of the NOS3 gene is associated with coronary spasm and vascular disease ( Casas et al, 2006 ; Kajiyama et al, 2000 ; Nakayama et al, 1999 ; Nakayama et al, 2000 ). Also, previous studies have demonstrated the association between this polymorphism and recurrent abortions and male infertility ( Luo et al, 2013 ; Safarinejad, Shafiei, & Safarinejad, 2010 ). This SNP significantly reduces NOS3 promoter transcription activity, inhibiting NO production which ends in endothelial dysfunction.…”

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

“…No association of this variant and RPL in a cohort of Tunisian had been reported [21]. Some other studies among different ethnicities after that had also reported similar ndings [22][23][24][25]. In contrast, in the study on the South Korean population had been discovered that − 786T-4b-894T haplotype signi cantly increased in the RPL group [23].…”