The Association of Mismatch Repair (MLH1) Gene Polymorphism with The Risk of Oligozoospermia in Iraqi Patients

  • Zaianab A. Kadhim , Ismail A. Abdul-Hassan


Oligozoospermia is a type of male infertility in which the number of sperms is under 15 million/ml, it is caused by different factors but it is mostly associated with idiopathic disorders. MLH1 is a part  of a genes system which codes for proteins responsible mainly for correcting  post  replicative DNA errors.rs1800734 is a single nucleotide polymorphism lies in the MLH1 CpG island at -93 from the translation start site while rs4647269 is an intron variant that lies in intron 9 . ). Blood and semen samples were collected from Baghdad Specialist Fertility Centre through the period from 1st of August 2018 until the end of February 2019 and the study was carried out in the Laboratories of Institute of Genetic Engineering and Biotechnology for Postgraduate Studies - University of Baghdad .Genotyping of  MLH1 gene for  SNPs rs1800743 and rs4647269  was done using Taqman genotyping assay by RT-PCR. Hormonal analysis was performed by using fluorescence immunoassay (FIA) on AFIAS autoanalyzer .The study showed that There were no significant differences between healthy and oligozoospermia patients in any of the genotypes of the SNP rs1800734, hence the SNP have no connection to the infertility incidence. As for rs4647269, The results showed that the CC genotype of rs4647269 was significantly higher ( p<0.05) in healthy patient (15(30%) versus 9 (18%) in oligozoospermia patient contrary to TT genotype that was significantly higher in oligozoospermia patients15 (30%) versus 7(14%).The heterozygous genotype CT had no significance between the two groups.Seminal fluid analysis showed a significant( p<0.05)  decrease in sperm count (9.65 ± 0.89) ,motility(24.34 ± 2.072)  ,activity8.06 ± 1.15 and normal sperms(4.60 ± 0.66) in the oligozoospermia patients .In oligozoospermia patients, mutant genotype TT of the SNP rs4647269showed a significance increase (P<0.05), compared to the wild genotype CC. Effect of SNP  rs4647269  on FSH appear in the wild and heterozygous  genotypes  as an increase in oligozoospermia patients compared to the healthy ones.In rs4647269 there was a significant increase (P<0.05) in prolactin in both the wild and the mutant genotypes of the oligozoospermia patients compared to the control, only the heterozygous resulted in a significant (P<0.05) decrease in the oligozoospermia patients.only the wild genotype CC showed a significant decrease (P<0.05) in testosterone concentration of oligozoospermia patients.the results of rs1800734 showed that the only genotype that showed a significant difference in LH levels between oligozoospermia  patients and control is  GA genotype (P<0.05). FSH results were significantly higher (P<0.01) in oligozoospermia patients of the genotype GG than control of the same genotype..  The results show a significant increase (P<0.01)  in PRL levels that accompanied the GG genotype in oligozoospermia patient. While the mutant genotype AA resulted in a significant decrease (P<0.05) in oligozoospermia patients. Only GG genotypes (the wild genotypes) showed a significant decrease (P<0.05) in testosterone concentration of oligozoospermia patients . This study have observed 4 possible haplotypes, GC hablotype was the most common in both groups (patients and controls)  and it was significantly higher( p<0.05)  in control. Also the GT hablotype was higher( p<0.05)  in oligozoospermia patients than healthy controls. 5 of 8 possible haplotype combinations showed no statistically significant differences between oligozoospermia  patients and control groups.This study concluded that 1. Both rs1800734 and rs4647269 SNPs of MLH1 gene have no role in the incidence of oligozoospermia in Iraqi men.