Association of genetic variants in CFTR gene, IVS8 c.1210-12T[5_9] and c.1210-35_1210-12GT[8_12], with spermatogenetic failure: case-control study and meta-analysis

It has been proposed that the genetic variants of IVS8 c.1210-12T5_9] and adjacent c.1210-35_1210-12GT8_12] in cystic fibrosis transmembrane conductance regulator gene might contribute to the spermatogenetic failure, but numerous genetic association studies that aimed to test this hypothesis reported conflicting results. So, in order to clarify such inconsistencies, we first conducted an original case-control study in Chinese Han population that consisted of 126 non-obstructive azoospermia, 169 severe oligospermia and 213 fertile male controls, and subsequently performed a meta-analysis of the available data, including our results. Our case-control study revealed that the frequencies of the T5] allele and the T5]+GT12] combination in patients with non-obstructive azoospermia were both significantly higher than those in the fertile controls (13.1 versus 2.8%, P<0.01; 97.0 versus 41.7%, P<0.01, respectively), thus indicating a high risk susceptibility to non-obstructive azoospermia for males with T5] allele or T5]+GT12]. However, as for the patients with severe oligospermia, both the T5] allele frequency and T5]+GT12] did not differ from that for the control subjects (4.4 versus 2.8%, P>0.01; 53.3 versus 41.7%, P>0.01, respectively). In addition, our meta-analysis showed a significant increased risk of non-obstructive azoospermia for males with T5] allele odds ratio (OR) 3.45, 95% confidence intervals (CI) 2.29-5.20, P=0.000] and T5]+GT12] (OR 7.57, 95% CI 2.53-22.65, P=0.000) compared with males carrying other alleles. By contrast, neither T5] allele itself nor T5]+GT12] combination had any effects on the risk of severe oligospermia (OR 0.96, 95% CI 0.42-2.21, P=0.002; OR 1.33, 95% CI 0.64-2.76, P=0.447). On the basis of these results, it can be concluded that the T5] allele itself, or in combination with GT12] repeat, may increase the susceptibility risk of non-obstructive azoospermia, but not that of severe oligospermia.