背景:为了阐明母体载脂蛋白E(ApoE)基因型的作用和复发性妊娠丢失(RPL)的风险,我们在此进行了更新的系统综述和荟萃分析,以重新评估有关此关联的证据.
方法:在PubMed上进行了全面的文献检索,截至2022年9月,WebofKnowledge和Cochrane图书馆。使用纽卡斯尔-渥太华量表评估方法学研究质量,并通过假阳性报告概率和贝叶斯错误发现概率来估计显着的合并比值比(OR)的可信度。
结果:2009年至2022年发表的12项研究符合纳入标准。在总体分析中,与ε3等位基因相比,ε4等位基因可增加RPL的风险(OR1.60,95%CI1.00-2.55,p=0.049),而携带ApoEε4等位基因的女性与携带ε2和ε3等位基因的女性相比,RPL的风险更高(OR1.75,95%CI1.06-2.87,p=0.028)。基于受试者种族的亚组分析显示,这些关联仅限于亚洲人群(ε4等位基因与ε3等位基因,OR5.93,95%CI1.79-19.61,p=0.004;ε4等位基因携带者与ε2和ε3等位基因的携带者,OR8.42,95%CI1.47-48.12,p=0.017)。在先验概率为0.001的假阳性报告概率或贝叶斯错误发现概率下,没有发现检测到的关联值得注意。
结论:这项更新的荟萃分析强调了亚洲人母体ApoE基因型与RPL风险之间的关联,但不是在高加索人。必须对亚裔女性进行进一步的病例对照研究,以排除假阳性结果的可能性。
In order to clarify the role of the maternal apolipoprotein E (ApoE) genotype and the risk of recurrent pregnancy loss (RPL), we herein performed an updated systematic
review and meta-analysis to reevaluate the evidence on this association.
A comprehensive literature search was performed on PubMed, Web of Knowledge and the Cochrane library up to September 2022. Methodological study quality was assessed using the Newcastle-Ottawa Scale and the credibility of significant pooled odds ratios (ORs) was estimated by the false positive report probability and the Bayesian false discovery probability.
Twelve studies published from 2009 to 2022 fulfilled the inclusion criteria. In the overall analysis, the ε4 allele was found to confer an increased risk of RPL compared to the ε3 allele (OR 1.60, 95% CI 1.00-2.55, p = 0.049) and women carrying the ApoE ε4 allele displayed a higher risk of RPL compared with those carrying the ε2 and ε3 alleles (OR 1.75, 95% CI 1.06-2.87, p = 0.028). Subgroup analysis based on subjects\' ethnicity revealed that these associations were restricted to the Asian population (ε4 allele vs. ε3 allele, OR 5.93, 95% CI 1.79-19.61, p = 0.004; ε4 allele carriers vs. carriers of ε2 and ε3 alleles, OR 8.42, 95% CI 1.47-48.12, p = 0.017). None of the associations detected were found to be noteworthy under false positive report probability or Bayesian false discovery probability at a prior probability of 0.001.
This updated meta-analysis highlights an association between maternal ApoE genotype and RPL risk in Asians, but not in Caucasians. Further case-control studies are warranted in women of Asian ancestry to exclude the possibility of false-positive findings.