Abstract
Study question
Do single nucleotide polymorphisms of the mitochondrial gene CYB (MT-CYB) affect male fertility?
Summary answer
there was a significant association between male fertility and rs527236194, rs28357373, and rs41504845 single nucleotide polymorphisms of the mitochondrial gene CYB (MT-CYB).
What is known already
Male infertility can be occurred as a result of various factors. However, genetic factors are detected in 15% of male infertility cases and can be classified into two groups: chromosomal abnormalities and single gene mutations. Sperm mitochondrial DNA alterations may have serious effects on spermatogenesis, sperm motility and the ability of sperm to fertilize the oocyte. Mutations of the MT-CYB gene might lead to various disorders and deficiencies specially in complex III which might interrupt in the ATP production process. Study design, size, duration: 111 semen samples were included in this prospectively designed study which carried out between 2017 and August 2019. Participants/materials, setting, methods: This study carried out at the Department of Obstetrics and Gynecology at Saarland University, Germany. Samples were divided into 67 subfertile “cases” and 44 fertile “control” groups.
After preparation of semen samples by density gradient centrifugation, nuclear and mitochondrial DNA (MT-DNA) was extracted using QIAamp DNA Mini Kit from QIAGEN. Thereafter, the MT-DNA was amplified using REPLI-g Mitochondrial DNA Kit from QIAGEN, followed by PCR and Sanger sequencing steps.
Main results and the role of chance
A total of 13 single nucleotide polymorphisms (SNPs) in the MT-CYB gene in each of the case and control groups were detected. Eight SNPs were non-synonymous variants including: rs2853508, rs28357685, rs41518645, rs2853507, rs28357376, rs35070048, rs2853506, and rs28660155 and five SNPs were synonymous variants: rs527236194, rs28357373, rs28357369, rs41504845, and rs2854124.Among these SNPs, three of them showed a significant difference in the genotype’s frequency test between sub-fertile and fertile groups: rs527236194 (T15784C; P = 0.0005), rs28357373 (T15629C; P = 0.0439), and rs41504845 (C15833T; P = 0.0038). For the allele’s frequency test, two SNPs were significant: rs527236194 (T15784C; P = 0.0014) and rs41504845 (C15833T; P = 0.0147).
Limitations, reasons for caution
The study population size
Wider implications of the findings: A larger prospective study will be required to confirm the associations between these mitochondrial gene polymorphisms in MT-CYB (rs527236194, rs28357373, rs41504845) and male infertility and to clarify the definite effect of the mitochondrial genetic variations on male infertility.
Trial registration number
Not applicable
Discovery of Three Newly Described Single Nucleotide Polymorphisms in Mitochondrial DNA Hypervariable Region I (HVI) and Estimation of Variants and Haplotypes Encompassing Nucleotide Positions 16024- 16365
