Androgen receptor (AR)-CAG trinucleotide repeat length and idiopathic male infertility: a case-control trial and a meta-analysis

CAG trinucleotide repeats in androgen receptor (AR) gene encode a polyglutamine tract in AR N-terminal transactivation domain. Studies have been conducted to evaluate the effect of CAG repeat length on male infertility, which have yielded contradictory results. This study aimed to explore the number of AR-CAG repeats in 150 fertile controls and 150 idiopathic infertile men, divided into four azoospermia, oligozoospermia, asthenozoospermia, and teratozoospermia subgroups. In addition, a meta-analysis was conducted based on previous studies to assess the association of the mentioned variation with male infertility in recent years. Polymerase chain reaction (PCR) targeting followed by an electrophoresis on polyacrylamide gel was used for AR-CAG genotype detecting. Moreover, a systematic search was performed in PubMed, Web of Science, Science Direct, and Google Scholar databases to collect eligible studies for meta-analysis purpose. According to the results, a significant association was observed between increased length of AR-CAG polymorphism and male infertility (p< 0.0001). Furthermore, there were similar significant associations in the azoospermia (p= 0.048), asthenozoospermia (p= 0.013) and teratozoospermia (p= 0.002) subgroups. In addition, meta-analysis on forty studies showed a significant association between AR-CAG polymorphism in the overall analysis (SMD= 0.199, 95 % CI= 0.112-0.287, p<0.001) and the Caucasian subgroup (SMD= 0.151, 95 % CI= 0.040-0.263, p= 0.008). Our results elucidated that long stretches of CAG repeat might lead to AR dysfunction, contributing to male infertility especially in the Caucasian population.