Mitochondrial nicotinamide adenine dinucleotide hydride dehydrogenase (NADH) subunit 4 (MTND4) polymorphisms and their association with male infertility

Purpose The purpose of the present study was to determine the relationship between infertility and the polymorphisms of mitochondrial NADH dehydrogenase subunit 4 (MTND4) by spermatozoa analysis in fertile and subfertile men. Methods Samples were divided into 68 subfertile men (case group) and 44 fertile men (control group). After semen analysis, samples were purified. The whole genome was extracted using a QIAamp DNA Mini Kit and the mitochondrial DNA was amplified by using the REPLI-g Mitochondrial DNA Kit. Polymerase chain reaction (PCR) was used to amplify the MT-ND4 gene. Then, samples were purified and sequenced using the Sanger method. Results Twenty-five single-nucleotide polymorphisms (SNPs) were identified in the MTND4 gene. The genotype frequencies of the study population showed a statistically significant association between rs2853495 G>A (Gly320Gly) and male infertility (P = 0.0351). Similarly, the allele frequency test showed that rs2853495 G>A (Gly320Gly) and rs869096886 A>G (Leu164Leu) were significantly associated with male infertility (adjusted OR = 2.616, 95% CI = 1.374–4.983, P = 0.002; adjusted OR = 2.237, 95% CI = 1.245–4.017, P = 0.007, respectively). Conclusion In conclusion, our findings suggested that male infertility was correlated with rs2853495 and rs869096886 SNPs in MTND4

The association between Mitochondrial NADH Dehydrogenase (MTND3, MTND4L, MTND4) polymorphisms and male infertility

Male infertility has been related to many factors and about 15 - 30% of the cases are related to genetic predisposition. The purpose of the present study was to determine the relationship between infertility and the polymorphism of mitochondrial NADH dehydrogenase subunit 3, 4L, and 4 (MT-ND3, MT-ND4L, and MT-ND4) genes. Direct sequencing of the target genes in the mitochondrial DNA was carried out on semen samples of 68 subfertile and 44 fertile men. Forty single nucleotide polymorphisms in the MT-ND3, MT-ND4L, and MT-ND4 genes were identified and genotyped as follows: eight SNPs in MTND3 rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954, seven SNPs in MTND4L rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881, and twenty five SNPs in MTND4 in the cases and controls: rs2853495, rs2857284, rs2853496, rs2853497, rs3087901, rs2853493, rs2853490, rs3088053, rs2853491, rs2857285, rs28358282, rs28594904, rs28669780, rs28415973, rs28471078, rs55714831, rs28358283, rs75214962, rs28529320, rs2853494, rs28609979, rs28358286, rs28359168, rs28384199, and rs869096886. The genotypes frequencies of the study population showed that rs2853495 G>A (Gly320Gly) in the MT-ND4 gene was statistically associated with male infertility (P = 0.0351). In the allele frequency test, the results showed that rs2853495 G>A (Gly320Gly) and rs869096886 A>G (Leu164Leu) in MT-ND4 were significantly associated with male infertility (adjusted OR = 2.616, 95% CI = 1.374 - 4.983, P = 0.0028; adjusted OR = 2.237, 95% CI = 1.245 - 4.017, P = 0.0073, respectively). On the other hand, no statistically significant association difference was reported between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia, oligoteratozoospermia subgroups of subfertile males and the fertile ones. In conclusion, our findings suggested that male infertility was correlated to rs2853495 and rs869096886 SNPs in the MTND4 gene. More studies on the subfertile males in different populations are required to develop a clear understanding of the role of these SNPs in male infertility. In addition, functional studies will be very helpful to elucidate the molecular role of these SNPs in the function of these genes