eNOS geneT786C,G894Tand4a4bpolymorphisms and male infertility susceptibility: a meta-analysis

Abstract

OR, 3.18; 95% CI, 1.54-6.56; TC vs. TT: OR, 1.65; 95% CI, 1.27-2.03). However, no overall association was observed between the other two polymorphisms of eNOS (G894T and 4a4b) and male infertility. Stratified analysis showed that significantly strong association between T786C polymorphism and semen quality was present in all three types of male infertility (azoospermia, oligozoospermia and asthenozoospermia). In the subgroup analysis based on ethnicity, both T786C and 4a4b could influence the risk of male infertility in Asian and Caucasian. Further studies of polymorphisms of eNOS with their biological functions are needed to understand the role in the development of male infertility.

Genetic Landscape of Nonobstructive Azoospermia and New Perspectives for the Clinic

“…The main reasons for such inconsistency are (1) the extremely reduced case/control cohort sizes analysed, which had led most likely to many type I and II errors in statistical hypothesis testing, and (2) the poor clinical characterisation of the patients included. Replicated associations of NOA-specific candidate genes include AR (see above) [143,144], PIWIL4 (PIWI-like 4, MIM*610315, encoding a key molecule for retrotransposon silencing in the germ line) [145][146][147], MTHFR (methylenetetrahydrofolate reductase, MIM*607093; an important regulatory gene involved in folate metabolism) [148][149][150], MTR (5-methyltetrahydrofolate-homocysteine S-methyltransferase, MIM*156570; responsible for the regeneration of methionine from homocysteine by transferring of a methyl group) [149,151], NOS3 (nitric oxide synthase 3, MIM*163729; involved in the release of nitric oxide for the regulation of the reproductive function) [152,153], and H2BFWT (H2B histone family, member W, testis-specific, MIM*300507, a testis-specific histone variant gene related to spermatogenesis) [154][155][156].…”

The “Hitchhiker’s Guide to the Galaxy” of Endothelial Dysfunction Markers in Human Fertility

“…NO is supposed to be inversely related to sperm motility, to attend sperm acrosome reaction and capacitation process, and to regulate the Sertoli/germ cells ratio in the seminiferous epithelium, allowing the production of mature and functional sperms [ 118 , 120 , 121 , 122 ]. It is widely demonstrated that SNPs falling within the eNOS gene, located on the chromosome 7q36, modulate the expression of the enzyme and, in turn, NO production [ 123 ]. Some of these SNPs, such as the c.T786C (rs2070744), falling in the promoter region, the c.G894T (rs1799983) on exon 7, and a variable number of intron 4 tandem “4a4b repeats” (rs61722009) 124, have been associated with fertility and sperm morphology.…”

“…However, another study found that a specific c.T786C and c.G894T allelic variant was significantly associated with impaired sperm number, motility, morphology, and seminal glutathione peroxidase [ 128 ]. A recent meta-analysis detected only c.T786C eNOS SNP as a predictor of semen alterations, i.e., sperm concentration and motility, in a population of 3507 men [ 123 , 132 ]. Despite the existence of pathophysiological rationale and experimental evidence, rigorous association studies and functional demonstrations of the association between eNOS SNPs and infertility are still lacking.…”

Association of eNOS 27-bp VNTR, 894G>T and 786T>C polymorphisms with susceptibility to Legg-Calve-Perthes Disease in Iranian children

“…Three polymorphisms of the eNOS gene have been identified, including a T786C (rs2070744) polymorphism in the promoter region, a G894T (rs1799983) polymorphism in exon 7 and a variable number of tandem 4a4b repeats (rs61722009) in intron 4. 14,15 Studies results showed that each polymorphism can influence the expression or functional activity of eNOS enzyme. 16 Recently, Zhao et al have been carried out a study to investigate the relationship between eNOS-4b/a polymorphism and the risk of LCPD in a Chinese population.…”