Impact of CAG repeat length in the androgen receptor gene on male infertility – a meta-analysis

Abstract

CAG repeats are polymorphic nucleotide repeats present in the androgen receptor gene. Many studies have estimated the association between CAG repeat length and male infertility, but the conclusions are controversial. Previous meta-analyses have come to different conclusions; however, new studies have been published. An updated meta-analysis was conducted. PubMed, CBM, CNKI and Web of Science databases were systematically searched for studies published from 1 January 2000 to 1 October 2015. Case-control studies on the association between CAG repeat length and male infertility using appropriate methodology were included. Forty studies were selected, including 3858 cases and 3161 controls. Results showed statistically significantly longer CAG repeat length among cases compared with controls (SMD = 0.14; 95% CI, 0.02-0.26). Shorter repeat length was associated with a lower risk of male infertility compared with a longer repeat length in the overall analysis (OR = 0.79, 95% CI: 0.66-0.95). Moreover, CAG repeat length was associated with male infertility in Caucasian populations, but not Asian or Egyptian populations. Subgroup analysis revealed no significant difference in German populations, but CAG repeat length was associated with male infertility in China and the USA. There were no significant differences between cases and controls in azoospermia and severe oligozoospermia.

The number of CAG and GGN triplet repeats in the Androgen Receptor gene exert combinatorial effect on hormonal and sperm parameters in young men

“…Seminal clinical findings linked abnormally expanded CAG tract (>40 repeats) with reduced fertility and low sperm counts (La Spada et al, 1991). The association was further supported by the most recent meta-analysis including 40 studies (3858 cases and 3161 controls) published from 2000 to 2015 (Xiao et al, 2016). The association was further supported by the most recent meta-analysis including 40 studies (3858 cases and 3161 controls) published from 2000 to 2015 (Xiao et al, 2016).…”

“…Meta-analysis across~4000 fertile and infertile men of European origin has reported that the carriers of a prevalent allele with 22 CAG repeats have a lower risk for developing infertility compared to the men with longer and shorter repeats (Nenonen et al, 2011). The association was further supported by the most recent meta-analysis including 40 studies (3858 cases and 3161 controls) published from 2000 to 2015 (Xiao et al, 2016). Regarding the AR GGN-repeat tract, in vitro studies have shown that the most common variant (GGN n = 23) exhibits the highest transactivating capacity when compared with shorter or longer GGN stretches (Lundin et al, 2007).…”

Efficacy of fibrin glue versus sutures for attaching conjunctival autografts in pterygium surgery: a systematic review with meta-analysis and trial sequential analysis of evidence

“…$\sqrt{\frac{{(Max-Mean)}^2+{(Min-Mean)}^2}{4}}$ Differences in recurrence rate and complication rate between the FG and suture groups were evaluated by OR with 95% CI, and SMD with 95% CI were used to estimate the difference in surgical duration between groups. We used the I 2 -statistic to calculate heterogeneity among the studies [48], I 2 > 50% implies significant heterogeneity resulting in the use of a random-effects model, otherwise a fixed-effects model was selected [24]. Due to the significant heterogeneity caused by a combination of different complications in the meta-analysis, we chosen a random-effects model to investigate complication rate.…”

“…Furthermore, the extent to which differences in the study region, patients and inconsistencies in case and control inclusion criteria between studies explain the conflicting outcomes is unknown. Therefore, meta-analysis provides a useful tool for the measurement of heterogeneity [24]. In fact, two published meta-analyses compared the efficacy of FG versus sutures in pterygium surgery in 2011.…”

The X chromosome and male infertility

“…The association between the AR-CAG repeat and male infertility has been intensively studied, but effects seem to be small and are still debated. Longer CAG repeat lengths may be a risk factor for male infertility, although population studies with variation detection in healthy controls argue against a strong association with unexplained male infertility, as concluded from large meta-analyses (Davis-Dao et al 2007;Xiao et al 2016). The transactivation domain of the AR comprises a further polyglycine tract (10-30 in length) encoded by a repeat consisting of GGN trinucleotides.…”