【摘要】：背景:子宫内膜异位症是一种常见的慢性妇科疾病,对女性健康造成显着的负面影响。 Wilms 肿瘤 1 相关蛋白 (WTAP) 是 N6-甲基腺苷修饰 RNA 甲基转移酶复合物的重要组成部分，在多种人类疾病中发挥着关键作用。然而，WTAP 基因的单核苷酸多态性 (SNP) 是否会导致子宫内膜异位症风险仍有待研究。方法：我们使用 Agena Bioscience MassArray iPLEX 平台对 473 名卵巢子宫内膜异位症患者和 459 名对照参与者的三种 WTAP 多态性进行了基因分型。利用逻辑回归模型评估 WTAP SNP 与卵巢子宫内膜异位症风险之间的关联。结果：在单基因座分析中，我们发现 rs1853259 G 变异基因型显着增加，而 rs7766006 T 变异基因型显着降低与卵巢子宫内膜异位症风险的关联。联合分析表明，具有两种不利基因型的个体比具有零风险基因型的个体表现出显着更高的卵巢子宫内膜异位症风险（调整后OR = 1.71 [1.23-2.37]，p = 0.001）。在分层分析中，rs1853259 AG/GG和rs7766006 GG基因型的风险效应在年龄≤30岁、妊娠≤1、产次≤1、rASRM I期的亚组中明显，而rs7766006 GG基因型与更差的风险相关（ rASRM II III IV 期患者的调整后 OR = 1.64 [1.08-2.48]，p = 0.021）。单倍型分析表明，具有GGG单倍型的个体比野生型AGG单倍型携带者患卵巢子宫内膜异位症的风险更高。此外，误报概率和贝叶斯错误发现概率分析验证了显着结果的可靠性。数量表达性状位点分析显示rs1853259和rs7766006与WTAP的表达水平相关。结论：我们的研究结果表明，WTAP 多态性与中国女性卵巢子宫内膜异位症的易感性相关。版权所有 © 2023 Wan、Ye、Chen、Xiong、OuYang、Wu、He、Duan、Jie、Zhang 和 Hua。

Background: Endometriosis is a common chronic gynecologic disorder with a significant negative impact on women's health. Wilms tumor 1-associated protein (WTAP) is a vital component of the RNA methyltransferase complex for N6-methyladenosine modification and plays a critical role in various human diseases. However, whether single nucleotide polymorphisms (SNPs) of the WTAP gene predispose to endometriosis risk remains to be investigated. Methods: We genotyped three WTAP polymorphisms in 473 ovarian endometriosis patients and 459 control participants using the Agena Bioscience MassArray iPLEX platform. The logistic regression models were utilized to assess the associations between WTAP SNPs and the risk of ovarian endometriosis. Results: In the single-locus analyses, we found that the rs1853259 G variant genotypes significantly increased, while the rs7766006 T variant genotypes significantly decreased the association with ovarian endometriosis risk. Combined analysis indicated that individuals with two unfavorable genotypes showed significantly higher ovarian endometriosis risk (adjusted OR = 1.71 [1.23-2.37], p = 0.001) than those with zero risk genotypes. In the stratified analysis, the risk effect of the rs1853259 AG/GG and rs7766006 GG genotypes was evident in subgroups of age ≤30, gravidity≤1, parity≤1, rASRM stage I, and the rs7766006 GG genotype was associated with worse risk (adjusted OR = 1.64 [1.08-2.48], p = 0.021) in the patients with rASRM stage II + III + IV. The haplotype analysis indicated that individuals with GGG haplotypes had a higher risk of ovarian endometriosis than wild-type AGG haplotype carriers. Moreover, false positive report probability and Bayesian false discovery probability analysis validated the reliability of the significant results. The quantitative expression trait loci analysis revealed that rs1853259 and rs7766006 were correlated with the expression levels of WTAP. Conclusion: Our findings demonstrated that WTAP polymorphisms were associated with susceptibility to ovarian endometriosis among Chinese women.Copyright © 2023 Wan, Ye, Chen, Xiong, OuYang, Wu, He, Duan, Jie, Zhang and Hua.