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.1210-12T[5_9] and adjacent c.1210-35_1210-12GT[8_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 T[5] allele and the T[5]+GT[12] 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 T[5] allele or T[5]+GT[12]. However, as for the patients with severe oligospermia, both the T[5] allele frequency and T[5]+GT[12] 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 T[5] allele [odds ratio (OR) 3.45, 95% confidence intervals (CI) 2.29-5.20, P=0.000] and T[5]+GT[12] (OR 7.57, 95% CI 2.53-22.65, P=0.000) compared with males carrying other alleles. By contrast, neither T[5] allele itself nor T[5]+GT[12] 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 T[5] allele itself, or in combination with GT[12] repeat, may increase the susceptibility risk of non-obstructive azoospermia, but not that of severe oligospermia.