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外周血白细胞端粒长度与子宫内膜异位症:一项孟德尔随机化研究。

Peripheral blood leukocyte Telomere length and endometriosis: A Mendelian randomization study.

作者信息

Wang Ying, Sun Fenyong, Yue Chaoyan, Man Qiuhong

机构信息

Department of Clinical Laboratory, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Department of Clinical Laboratory, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

出版信息

Heliyon. 2024 Jun 27;10(14):e33854. doi: 10.1016/j.heliyon.2024.e33854. eCollection 2024 Jul 30.

Abstract

BACKGROUND

The link between peripheral blood leukocyte telomere length (LTL) and endometriosis has remained uncertain. In order to investigate this association, a two-sample Mendelian randomization(MR) analysis was performed.

METHODS

We extracted Single-nucleotide polymorphisms (SNPs) associated with LTL from a published genome-wide association study (GWAS) comprising 472,174 individuals. Data on endometriosis, including its seven subtypes, were sourced from the iue open gwas project. Four methods were employed for MR: Inverse-variance weighted analysis (IVW), Mendelian randomization-Egger regression (MR Egger), weighted-median analysis, and Weighted Mode.

RESULTS

Genetically determined LTL was identified as a factor that can promote the occurrence of endometriosis. With every 1-SD increase in LTL, the risk of endometriosis increased by 26 % (OR = 1.260, 95 % CI = 1.073 to 1.479;  = 0.005). Genetically determined LTL also contributed to endometriosis subtypes: intestine (OR = 3.584, 95 % CI = 1.597 to 8.041;  = 0.002), ovary (OR = 1.308, 95 % CI = 1.033 to 1.655;  = 0.026), rectovaginal septum and vagina (OR = 1.360, 95 % CI = 1.000 to 1.851;  = 0.049). There was no observed causal relationship between LTL and the other four subtypes.

CONCLUSION

This study, utilizing genetic data, offers evidence that longer LTL may cause increased risks of endometriosis, specifically endometriosis of the intestine, ovary, rectovaginal septum and vagina. These findings not only suggest that LTL may serve as a predictive factor for assessing the prevalence of three endometriosis subtypes but also provide new insights into the study of endometriosis pathogenesis.

摘要

背景

外周血白细胞端粒长度(LTL)与子宫内膜异位症之间的联系尚不确定。为了研究这种关联,我们进行了一项两样本孟德尔随机化(MR)分析。

方法

我们从一项包含472,174名个体的已发表全基因组关联研究(GWAS)中提取了与LTL相关的单核苷酸多态性(SNP)。关于子宫内膜异位症的数据,包括其七种亚型,来自国际子宫内异症开放GWAS项目。我们采用了四种方法进行MR分析:逆方差加权分析(IVW)、孟德尔随机化-伊格回归(MR Egger)、加权中位数分析和加权模式分析。

结果

遗传决定的LTL被确定为可促进子宫内膜异位症发生的一个因素。LTL每增加1个标准差,子宫内膜异位症的风险增加26%(OR = 1.260,95% CI = 1.073至1.479;P = 0.005)。遗传决定的LTL也与子宫内膜异位症的亚型有关:肠道型(OR = 3.584,95% CI = 1.597至8.041;P = 0.002)、卵巢型(OR = 1.308,95% CI = 1.033至1.655;P = 0.026)、直肠阴道隔和阴道型(OR = 1.360,95% CI = 1.000至1.851;P = 0.049)。未观察到LTL与其他四种亚型之间存在因果关系。

结论

本研究利用遗传数据提供了证据,表明较长的LTL可能会增加子宫内膜异位症的风险,特别是肠道、卵巢、直肠阴道隔和阴道的子宫内膜异位症。这些发现不仅表明LTL可作为评估三种子宫内膜异位症亚型患病率的预测因素,也为子宫内膜异位症发病机制的研究提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b7/11295982/d72a32fd5474/gr1.jpg

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