CAG-repeats Variant In The POLG Gene And Male Infertility

Male infertility is a multi-factorial syndrome encompassing a wide variety of disorders. Approximately 15 percent of couples are infertile, and among these couples, male factor infertility accounts for approximately 50 percent of causes. DNA polymerase y (POLG), which is encoded by the POLG gene, is the only known DNA polymerase for mtDNA replication and maintenance in human beings. The human POLG gene is located on 15q24-15q26, spans 23 exons, and includes a trinucleotide CAG-repeat region which encodes a polyglutamine stretch near the N-terminus of the mature protein and downstream of the presumed mitochondrial targeting sequence. It has been reported that human cDNA sequences contain 10 consecutive glutamines encoding CAG codons, followed by a single glutamine encoding a CAA codon, and two further CAG codons. Polyglutamine tracts can be sites of protein-protein interactions; altering the tract in POLG may result in suboptimal or improper mtDNA replication. To date over 150 disease mutations and 9 nonsynonymous polymorphisms in POLG have been found to be associated with autosomal recessive and dominant diseases.Meta-analysis is a statistical method of large collection of analysis results from individual studies for the purpose of integrating the findings. Meta-analysis enable us to report that the effect is robust across the kinds of populations sampled, and also to estimate the magnitude of the effect more precisely than we could with any of the studies alone.Several reports have implicated a association between the length of CAG-repeat in the polymerase y gene (pol y) and male infertility. However, such results have not been reproduced in other studies. In the present study, POLG-CAG repeat were analyzed in 535 healthy individuals from 6 Chinese Han populations living in different provinces. The frequencies of 10-CAG alleles and genotypes were 97.38% and 94.13%respectively; however, there was no significant difference among the 6 Chinese Han populations. We performed a pairwise comparison of different populations previously published on the frequency of the CAG-repeats genotype and found differences in the frequency of the three POLG CAG-repeats genotype between geographically-and ethnically-related populations. The prevalence of homozygous wild type (10/10) was shown to be exceedingly high in Chinese (97.38%). These results indicated that there is a significant difference in frequencies of the three CAG-repeat genotypes among different populations. Further, we determined the distribution of POLG-CAG repeat in 367 infertile men and 323 fertile men. Our study suggested that the distribution of POLG-CAG repeat alleles and genotypes were not significantly different between infertile (95.67%and 92.67%) and fertile men (97.22%and 94.44%). In a subsequent Meta-analysis combining our data with previous studies, a comparison of CAG-repeat alleles showed there was no obvious association with male infertility (pooled OR=0.94; 95%CI:0.60-1.48). The lack of significance appeared after combined genotypes with the following genetic models: homozygote comparison, heterozygote comparison, dominant model comparison, and recessive genetic comparison. In conclusion, the frequencies of POLG CAG-repeat variants are quite different in diverse ethnicities and this polymorphism may not be associated with Chinese male infertility. Based on a subsequent Meta-analysis, there was no obvious association between CAG-repeat variants of the POLG gene and male infertility.