Role of Androgen Receptor CAG Repeat Polymorphism and X-Inactivation in the Manifestation of Recurrent Spontaneous Abortions in Indian Women

Abstract

The aim of the present study was to investigate the role of CAG repeat polymorphism and X-chromosome Inactivation (XCI) pattern in Recurrent Spontaneous Abortions among Indian women which has not been hitherto explored. 117 RSA cases and 224 Controls were included in the study. Cases were recruited from two different hospitals - Lakshmi Fertility Clinic, Nellore and Fernandez Maternity Hospital, Hyderabad. Controls were roughly matched for age, ethnicity and socioeconomic status. The CAG repeats of the Androgen Receptor gene were genotyped using a PCR-based assay and were analysed using the GeneMapper software to determine the CAG repeat length. XCI analysis was also carried out to assess the inactivation percentages. RSA cases had a significantly greater frequency of allele sizes in the polymorphic range above 19 repeats (p = 0.006), which is the median value of the controls, and in the biallelic mean range above 21 repeats (p = 0.002). We found no evidence of abnormal incidence of skewed X-inactivation. We conclude that longer CAG repeat lengths are associated with increased odds for RSA with statistical power estimated to be ∼90%.

Androgen receptor (AR) gene CAG trinucleotide repeat length associated with body composition measures in non-syndromic obese, non-obese and Prader-Willi syndrome individuals

“…This may lead to better management options and eventually prevention strategies for obesity and possibly lessen infertility. Androgen responsivity secondary to AR gene CAG repeat length has a multi-level influence on human reproduction and fertility through effects on male testicular development and spermatogenesis [27,28] and female pregnancy outcomes [29]. Our study further reports male stature and female weight as androgen responsive modulatory variables with potential influence on fertility.…”

“…Diminished in vivo androgenicity in males leads to decreased spermatogenesis and smaller seminal vesicles [24][25][26][27] thereby impacting fertility and human reproduction [28]. AR gene CAG repeat lengths above 21 correlate with poor pregnancy outcomes in females and recurrent spontaneous abortions [29]. Androgen receptor gene CAG repeat length is also associated with ovarian reserve and may play a role in ovulation but the natural ovarian aging process does not appear to affect ovarian response to gonadotropins [30].…”

Association of skewed X chromosome inactivation and idiopathic recurrent spontaneous abortion: a systematic review and meta-analysis

“…Seven studies showed an increased highly SXCI in patients who had experienced RSA compared with the control group (Bagislar et al, 2006;Beever et al, 2003;Dasoula et al, 2008;Hogge et al, 2007;Kuo et al, 2008;Sullivan et al, 2003;Uehara et al, 2001), whereas the other five reported lower prevalence of SXCI in cases of RSA than in normal females (Aruna et al, 2011;Kaare et al, 2008;Kim et al, 2004;Pasquier et al, 2007;Warburton et al, 2009). Random effect model was used for the heterogeneity test showed P = 0.004, and results of meta-analyses result showed no significant difference in the incidence of SXCI in cases of RSA and controls (OR = 1.58 [0.83 to 3.01]) (Figure 2).…”

“…Full manuscripts were obtained for the remaining 19 articles for detailed evaluation; after scrutiny, four articles were excluded as they were reviews, three studies (Lanasa et al, 1999(Lanasa et al, , 2001Sangha et al, 1999) were excluded for the duplication of population. Twelve case-control studies (Aruna et al, 2011;Bagislar et al, 2006;Beever et al, 2003;Dasoula et al, 2008;Hogge et al, 2007;Kaare et al, 2008;Kim et al, 2004;Kuo et al, 2008;Pasquier et al, 2007;Sullivan et al, 2003;Uehara et al, 2001;Warburton et al, 2009) were, therefore, included in the meta-analysis, all in English and published as full text, with characteristics presented in Table 1.…”

Association of sex hormone receptor gene polymorphisms with recurrent pregnancy loss: a systematic review and meta-analysis

“…The expansion of CAG repeats, coding for a polyglutamine (polyQ) tract in the N-terminal domain, leads to an increased transactivation function (21). Several clinical conditions had been shown to be associated with the length of CAG repeats in the AR gene (22)(23)(24)(25)(26).…”