rs1800734: a risk allele for nonobstructive azoospermia related to maturation arrest
Abstract
Background: Male infertility is increasingly being conceived as a biomarker of general male health status other than being a significant reproductive health issue. Nonobstructive azoospermia (NOA) patients have the worst health status impairment as well as highest risk of developing cancer. It’s well known that cancer susceptibility gene, MLH1 have roles in homologous recombination during meiosis. Mlh1 mutant mice have azoospermia with meiotic arrest.
Aim: We aimed to identify risk alleles in MLH1 gene in males with nonobstructive azoospermia related maturation arrest (MA) to investigate further whether this cancer susceptibility gene is also related to male infertility.
Patients and Methods: MLH1 variants were genotyped in 42 patients with MA. The variants of interest then compared to GnomAD v.3.1.2 (non-cancer) male population database and to the repository exome data of a national genetic disease evaluation center (NGDEC).
Results: rs1800734 allele frequencies were significantly higher in the patient group compared to GnomAD (p<0.001) with odds ratio (OR):2.3 (1.5-3.5), and to the exome data of NGDEC (p=0.002) with OR:2 (1.3-3.1). Homozygous genotype for rs1800734 was significantly higher in the patient group compared to the GnomAD (p<0.001) with OR: 5 (2.24-11) and to the exome data (p=0.010) with OR: 3.3 (1.4-7.5).
Conclusion: In this study we found rs1800734 is a risk allele for NOA related to MA. It is known that rs1800734 is related to hypermethylation of MLH1 promoter. As MLH1 hypermethylation has been shown to be increased in oligozoospermic males, the same mechanism in carcinogenesis may also exist for azoospermia in the context of rs1800734.
Keywords
rs1800734, MLH1, nonobstructive azoospermia, maturation arrest, male infertility
Supporting Institution
TÜBİTAK
Project Number
220S004
Ethical Statement
The study protocol was approved by the Ethics Committee of Ankara University School of Medicine (reference number: İ4-210-20) and performed according to the Declaration of Helsinki.
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