孟德尔随机化
医学
内科学
胆固醇转移蛋白
胃肠病学
炎症性肠病
克罗恩病
胆固醇
溃疡性结肠炎
内分泌学
前蛋白转化酶
脂蛋白
疾病
低密度脂蛋白受体
生物
生物化学
基因
遗传变异
基因型
作者
Heqing Tao,Yu Zhou,Yongqiang Dong,Ligang Liu,Liang Peng,Xueqing Chen
标识
DOI:10.3389/fimmu.2023.1160312
摘要
Background To assess the causal role of lipid traits and lipid-lowering agents in inflammatory bowel disease (IBD). Methods Univariable mendelian randomization (MR) and multivariable MR (MVMR) analyses were conducted to evaluate the causal association between low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and IBD. Drug-targeted MR analyzed the effects of lipid-lowering drugs on IBD, and network MR was used to analyze potential mediation effects. Results The levels of HDL-C had an inverse relationship with the risk of Crohn’s disease (CD, OR: 0.85, 95% CI: 0.73-0.98, P = 0.024). In MVMR, the inverse relationships were found in all three outcomes. Drug-targeted MR analyses showed that with one-SD LDL-C decrease predicted by variants at or near proprotein convertase subtilisin/kexin type 9 ( PCSK9) , the OR values of people diagnosed with IBD, ulcerative colitis (UC) and CD were 1.75 (95%CI: 1.13-2.69, P = 0.011), 2.1 (95%CI: 1.28-3.42, P = 0.003) and 2.24 (95%CI: 1.11-4.5, P = 0.024), respectively. With one-SD LDL-C decrease predicted by variants at or near cholesteryl ester transfer protein (CETP) , the OR value of people diagnosed with CD was 0.12 (95%CI: 0.03-0.51, P = 0.004). Network-MR showed that HDL-C mediated the causal pathway from variants at or near CETP to CD. Conclusion Our study suggested a causal association between HDL-C and IBD, UC and CD. Genetically proxied inhibition of PCSK9 increased the risk of IBD, UC and CD, while inhibition of CETP decreased the risk of CD. Further studies are needed to clarify the long-term effect of lipid-lowering drugs on the gastrointestinal disorders.
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