CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): a systemic review and meta-analysis

Abstract

Numerous studies have reported CFTR mutations in CBAVD (congenital bilateral absence of the vas deferens) patients, but their results are not completely consistent. Here, we present a systemic review and meta-analysis with emphasis on clarifying further the genetic association of CFTR mutations with CBAVD. We searched the MEDLINE database until March, 2011 for eligible articles reporting CFTR mutations in CBAVD. Relevant data from each included study were abstracted by two independent reviewers. The overall frequency of CFTR mutations in CBAVD and the odds ratio (OR) for common specific alleles were pooled under random-effect or fixed-effect model as appropriate. Subgroup analysis was performed by ethnicity, and potential heterogeneity and bias were both assessed. Among CBAVD patients, 78% had at least one CFTR mutation, 46% having two and 28% only one. Moreover, the common heterozygous F508del/5T and F508del/R117H were observed in 17 and 4% of CBAVD cases respectively, and the allele frequency in CBAVD was 17% for F508del, 25% for 5T and 3% for R117H. Subgroup analysis indicated an increased frequency of cases with two mutations in Caucasian patients than in Non-Caucasian (68 versus 50%, P= 0.012), but no differences for cases with at least one mutation (88 versus 77%, P= 0.163) or with only one mutation (17 versus 25%, P= 0.115). Caucasian patients had higher F508del frequency, but lower 5T frequency, than Non-Caucasian (22 versus 8%, P= 0.001; 20 versus 31%, P= 0.009). Summary OR was 9.25 for 5T [95% confidence interval (CI) 7.07-12.11, P= 0.000], with moderate heterogeneity (I(2)= 49.20%, P= 0.019) and evident bias (Egger's test, P= 0.005), and it was 19.43 for 5T/(TG)12_13 (95% CI 10.48-30.03, P= 0.000) without any evidence of heterogeneity (I(2)= 0.1%, P= 0.391) and bias (Egger's test, P= 0.160). The OR for 5T/(TG)12_13 was significantly higher than that for 5T allele (P= 0.000). In summary, our results demonstrate a high frequency of CFTR mutations in CBAVD patients, and these exhibit evident ethnic differences. In addition, 5T allele and 5T/(TG)12_13 may contribute to the increased risk for CBAVD, with the 5T penetrance probably being modulated by adjacent (TG)12_13.