骨形态发生蛋白15基因多态性与早发性卵巢功能不全相关性荟萃分析

Relationship between polymorphisms of bone morphogenetic protein 15 gene and premature ovarian insufficiency:a meta-analysis update

目的探索骨形态发生蛋白15(bone morphogenetic protein 15,BMP15)基因多态性与早发性卵巢功能不全(premature ovarian insufficiency,POI)的相关性,为POI患者遗传咨询提供循证医学证据。方法运用计算机检索Pubmed、EMbase、Cochrane Library及中国期刊全文数据库中关于BMP15基因多态性及POI有关的病例对照研究或队列研究,检索时限是1950年1月至2022年12月。由2名研究者独立地根据纳入及排除标准进行文献筛选、数据提取及研究质量评价,采用RevMan5.3软件进行meta分析,P<0.05考虑有统计学意义。结果最终纳入17项研究,共3758例患者,其中POI组1631例患者,对照组2127例患者。meta分析显示,不管是全部地区还是亚洲地区,POI组患者的BMP15-9C>G、788insTCT及852C>T均与对照组相似,差异均无统计学意义(均P>0.05)。另外,尽管POI组患者的BMP15443T>C及308A>G多态性与对照组相似,差异均无统计学意义(均P>0.05),但POI组BMP15308A>G和443T>C的纯合突变率较对照组增加。POI组患者BMP15538G>A突变发生率较对照组增加,差异有统计学意义(基因型AA+AG与基因型GG相比,OR=6.48,95%CI:2.48~16.92,P<0.001;等位基因A与等位基因G相比,OR=7.61,95%CI:2.93~19.57,P<0.001)。结论BMP15538G>A突变与POI发病可能相关,携带BMP15538G>A突变的人群发生POI风险增加。未来仍需要不同种族的大样本量前瞻性队列研究来进一步证实BMP15基因变异与POI之间的关系。

Objective To systematically evaluate the relationship between polymorphisms of bone morphogenetic protein 15(BMP15)gene and premature ovarian insufficiency(POI),and to provide evidence-based medical evidences for genetic counseling of POI patients.Methods Case control studies or cohort studies related to BMP15 gene polymorphisms and POI in Pubmed,EMbase,Cochrane Library and Chinese Journal Full Text Database were systematically searched.All articles were published from January 1950 to December 2022.Two researchers independently performed literature screening,data extraction and research quality evaluation.RevMan5.3 software was used for meta-analysis.P<0.05 was considered statistically significant.Results The literature search yielded 17 studies with a total of 3758 patients,including 1631 patients in POI group and 2127 patients in control group.Meta-analysis showed that the polymorphisms of BMP15-9C>G,788insTCT and 852C>T in patients with POI were comparable to those in control group(P>0.05).In addition,although the polymorphisms of BMP15443T>C and 308A>G in patients with POI were comparable with those in control group(P>0.05),the homozygous mutation incidence of BMP15308A>G and 443T>C in patients with POI were higher than those in control group.The incidence of BMP15538G>A mutation in patients with POI was significantly higher than that in control group(genotype AA+AG vs.GG,OR=6.48,95%CI:2.48-16.92,P<0.001;allele A vs.G,OR=7.61,95%CI:2.93-19.57,P<0.001).Conclusion The polymorphism of BMP15538G>A may be related to the pathogenesis of POI,and 538G>A carriers may be prone to POI.Further well-designed studies with larger samples are required to confirm the association between BMP15 gene variants and POI.