CFTR gene mutations and polymorphism are associated with non-obstructive azoospermia: From case-control study

A variety of experimental studies have yielded evidence that the cystic fibrosis transmembrane conductance regulator (CFTR) protein participates in the process of spermatogenesis. However, the association between CFTR gene and non-obstructive azoospermia (NOA) disease remained to be a question. First, we reviewed available data from the PubMed and Embase databases before May 2016 to find the most common mutations of CFTR gene in NOA patients. Second, an original case-control study was conducted on NOA patients (n=100) and a control group consisting of fertile males (n=100), selected from August 2015 to March 2017, to detect CFTR gene mutations and polymorphism. Peripheral blood samples from NOA patients and normal controls were analyzed for the presence of specific sequences of CFTR gene by polymerase chain reaction amplification followed by direct sequencing. From our comprehensive review, 12 case-control studies were found concerning the relation between CFTR gene mutations and polymorphism and NOA disease. Fifty-four mutations were mentioned and IVS8 poly-T, TG repeats, F508del and R117H mutations were the most common ones. Based on that, we detected IVS8 poly-T, TG repeats, F508del, R117H and M470V mutations in our case control study. We found that the T5 allele was present at a significantly higher rate in NOA patients than in the control group (5.00% versus 0.00%, p<0.01) with increased risk having NOA [Odds ratios (OR) 2.05, 95% confidence intervals (CI) 1.85-2.27]. The T5 variant was always accompanied by TG12 (10/10) and V470 allele participated in most TG12T5 haplotypes (8/10). TG12T5-V470 haplotype also enhanced risk of having NOA [OR 2.04, 95% CI 1.84-2.26]. F508del and R117H mutations were not found in either group. In conclusion, the polyvariant mutant genes of CFTR: T5 allele and TG12-T5-V470 genotype are correlated with NOA, but F508del and R117H mutations have low possibility to be associated with NOA.