Pharmacogenetic study of Asn680Ser and -29A>G in FSHR gene in Chinese women undergoing controlled ovarian hyperstimulation

Xiaohe Sun, T. Ni, Guangyu Li, Jingjing Jiang, Junhao Yan, Zi-jiang Chen
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引用次数: 1

Abstract

Abstract The outcome of controlled ovarian hyperstimulation (COH) is various and unpredictable. According to previous studies, 2 single nucleotide polymorphisms, Asn680Ser and -29A/G, have a pharmacogenetic association with ovarian response to COH. However, studies on the Asn680Ser polymorphism have yielded inconsistent conclusions and only a few studies with small sample sizes have been performed on -29A/G. The association of these 2 polymorphisms with ovarian response remains unclear. The present study evaluated the association of Asn680Ser and -29A/G genotypes with COH. A total of 414 Chinese women undergoing in vitro fertilization-embryo transfer were included. Genotypes for these single nucleotide polymorphisms were identified by high-resolution melting-curve analysis. The value of exogenous follicle-stimulating hormone dosage per oocyte divided by the body surface area (Dosage/Oocyte × Surface) was calculated for each patient as an indicator of ovarian response. The results of statistical analyses showed no association between Asn680Ser genotype and ovarian response. As for -29A/G, heterozygote individuals had more oocytes retrieved (P = 0.034). Combinatorial analysis of these 2 single nucleotide polymorphisms showed that genotype A/G-Asn/Asn had lower basal-follicle-stimulating hormone and more oocytes retrieved. Analysis of genotype association with ovarian response also revealed this genotype had a significantly higher risk of developing hyper response (OR = 7.86; 95% CI: 1.31–9.43). To some extent, there were associations between the studied polymorphisms and ovarian response; however, the power of this link is weak and has limited value for clinical prediction.
中国控制性卵巢过度刺激女性FSHR基因Asn680Ser和-29A>G的药理学研究
控制性卵巢过度刺激(COH)的结果是多种多样且不可预测的。根据以往的研究,Asn680Ser和-29A/G这两个单核苷酸多态性与卵巢对COH的反应存在药物遗传学关联。然而,关于Asn680Ser多态性的研究得出了不一致的结论,仅对-29A/G进行了少量小样本量的研究。这两种多态性与卵巢反应的关系尚不清楚。本研究评估了Asn680Ser和-29A/G基因型与COH的关系。共纳入了414名接受体外受精-胚胎移植的中国妇女。这些单核苷酸多态性的基因型通过高分辨率熔融曲线分析确定。计算每位患者每卵母细胞外源性促卵泡激素剂量除以体表面积(剂量/卵母细胞×表面)的值,作为卵巢反应的指标。统计分析结果显示Asn680Ser基因型与卵巢反应无相关性。对于-29A/G,杂合子个体获得的卵母细胞较多(P = 0.034)。对这2个单核苷酸多态性的组合分析表明,基因型A/G-Asn/Asn具有较低的促卵泡激素和更多的卵母细胞。基因型与卵巢反应的相关性分析也显示,该基因型发生高反应的风险显著增加(OR = 7.86;95% ci: 1.31-9.43)。在某种程度上,所研究的多态性与卵巢反应之间存在关联;然而,这种联系的力量很弱,对临床预测的价值有限。
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