Association between the single nucleotide variants of the mitochondrial cytochrome B gene (MT-CYB) and the male infertility

Abstract

Background Idiopathic male infertility can be attributed to genetic predispositions that affect sperm performance and function. Genetic alterations in the mitochondrial DNA (mtDNA) have been linked to certain types of male infertility and abnormal sperm function. Mutations in the mitochondrial cytochrome B (MT-CYB) gene might lead to some deficiencies in mitochondrial function. Thus, in the current study, we aimed to investigate the effect of mutations in the MT-CYB gene on sperm motility and male infertility. Methods and results Semen specimens were collected from 111 men where 67 men were subfertile and 44 were fertile. QIAamp DNA Mini Kit and REPLI-g Mitochondrial DNA Kit from QIAGEN were used to isolate and amplify the mitochondrial DNA. Followed by PCR and Sanger sequencing for the target sequence in the MT-CYP gene. Sequencing of the MT-CYB gene revealed a total of thirteen single nucleotide polymorphisms (SNPs). Eight SNPs were non-synonymous variant (missense variant) including: rs2853508, rs28357685, rs41518645, rs2853507, rs28357376, rs35070048, rs2853506, and rs28660155. While five SNPs were Synonymous variant: rs527236194, rs28357373, rs28357369, rs41504845, and rs2854124. Among these SNPs, three variants showed a significant difference in the frequency of the genotypes between subfertile and fertile groups: rs527236194 (T15784C) (P = 0.0005), rs28357373 (T15629C) (P = 0.0439), and rs41504845 (C15833T) (P = 0.0038). Moreover, two SNPs showed a significant association between allelic frequencies of rs527236194 (T15784C) (P = 0.0014) and rs41504845 (C15833T) (P = 0.0147) and male subfertility. Conclusion The current study showed a significant association between the MT-CYB gene polymorphisms and the development of male infertility. In particular, rs527236194, rs28357373 and rs41504845 variants were found to be the most related to the subfertility group. Further studies on larger and other populations are required to reveal the exact role of this gene in the development of male infertility. In addition, functional studies will be helpful to elucidate the molecular impact of the MT-CYP polymorphisms on mitochondrial function.

A lack of a definite correlation between male sub-fertility and single nucleotide polymorphisms in sperm mitochondrial genes MT-CO3, MT-ATP6 and MT-ATP8

“…For instance, a recent study reported a significant correlation between polymorphisms of the MT-CYB gene and sub-fertility in men. Particularly, rs527236194, rs28357373 and rs41504845 variants were found significantly related to the sub-fertility group [ 29 ].…”

Mitochondrial DNA Missense Mutations ChrMT: 8981A > G and ChrMT: 6268C > T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein–Barr Virus

“…The isolated DNA was used for further selective purification and enrichment of mitochondrial ChrMT DNA using a REPLI-g Mitochondrial DNA Kit (Qiagen, Germantown, MD), based on the recommendation of the manufacturer. Briefly, the isolated DNA sample, from either the cells or the plasma pellet, was added to the REPLI-g reaction buffer mixed with REPLI-g human mitochondrial primers, preincubated at 75°C for 5 min, followed by adding DNA polymerase, incubating at 33°C for 8 hours, and then inactivation of the enzyme at 65°C for 3 min [ 19 , 20 ]. The ChrMT DNA was isolated from the cells (including WBCs/platelets) and the plasma ( Figure 2 ) and stored at −80°C before the sequencing analysis.…”

Semen Analysis and Infertility

“…It is physically associated with the inner mitochondrial membrane, where free oxygen radicals are generated [50]. Recently, an association was discovered between the single nucleotide variants of the mitochondria cytochrome B gene (MT-CYB) and male infertility [52].…”