Around 20–28% of FMR1gene CGG premutation (PM) carriers are at augmented risk towards an infertility related disorder, Fragile X-associated primary ovarian insufficiency (FXPOI). Except the effect of CGG repeats, reports are not available on the mechanism through which the cis-acting variations, namely, SNPs involved in POI susceptibility. Addressing the hypothesis that the FMR1 gene polymorphisms [CGG repeats, rs25731(T > A) and rs4949(A > G)] might increase their individual and combined impact in disease predisposition, we tested the genetic variants in 200 south Indian DNA samples consists of 100 patients and 100 healthy volunteers. We used gene scan method to score the CGG repeat length, and ARMS and RFLP methods to genotype the SNPs. Only 0.5% of each Gray zone and PM alleles were found among patient group, however, no disease association was noticed with repeat length. The rs25731 showed protection [OR:0.32; (0.13–0.76), p = 0.006] and rs4949 reported a 2.5-fold risk towards the disease predisposition [OR:2.46; (1.06–5.74), p = 0.031] but, both found insignificant after Bonferroni correction was done under different Genetic Models. Novel classification of genotype combinations, ‘Normal&Variant Homozygote’ [OR:2.89,(1.12–7.9), p < 0.05] and ‘Allele2-T-G’ haplotype block (6%vs.1%, p = 0.08) were noticed to be at marginal risk for POI. We demonstrated a susceptible role of the combined effect of variant allele-G and Allele-2 (repeat allele outside the normal range) for FXPOI. To support our findings of its first kind, further studies with large samples are warranted in understanding the role of FMR1 genetic variants in FXPOI etio-pathophysiology, the outcome might help in providing better reproductive treatment options for females, who are at risk for FXPOI.

FMR1基因CGG突变（PM）携带者中约20–28％罹患不育相关疾病（易碎X相关性原发性卵巢功能不全（FXPOI））的风险增加。除了CGG重复的影响外，尚无有关顺式作用变异（即参与POI敏感性的SNP）的机制的报道。解决FMR1的假设基因多态性[CGG重复，rs25731（T> A）和rs4949（A> G）]可能会增加其对疾病易感性的综合影响，我们在200例来自100名患者和100名健康志愿者的南印度DNA样本中测试了遗传变异。我们使用基因扫描方法对CGG重复序列长度进行评分，并使用ARMS和RFLP方法对SNP进行基因分型。每个灰色区域和PM的仅0.5％在患者组中发现了等位基因，但是没有发现重复长度与疾病相关。rs25731显示出保护[OR：0.32; （0.13-0.76），p = 0.006]，而rs4949报告该疾病易感性的风险为2.5倍[OR：2.46; （1.06-5.74），p = 0.031]，但在不同的遗传模型下进行Bonferroni校正后，两者均无意义。注意到新的基因型组合分类，“正常和变异纯合子” [OR：2.89，（1.12-7.9），p <0.05]和“等位基因2-T-G”单倍型基因组（6％vs.1％，p = 0.08） POI的边际风险。我们证明了变体等位基因G和等位基因2（对FXPOI重复超出正常范围的等位基因）。为了支持我们的第一类发现，有必要对大量样本进行进一步研究，以了解FMR1基因变异在FXPOI病因-病理生理中的作用，其结果可能有助于为有FXPOI风险的女性提供更好的生殖治疗选择。