Ma Xiao-Na, Shi Mei-Feng, Feng Wei, Chen Shu-Lin, Zhong Xiao-Qin, Lin Chang-Song, Xu Qiang
State Key Laboratory of Traditional Chinese Medicine Syndrome, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Department of Rheumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
ACS Omega. 2024 Jul 25;9(31):33826-33832. doi: 10.1021/acsomega.4c03483. eCollection 2024 Aug 6.
Previous studies have reported that the inappropriate use of allopurinol may increase the risk of cerebrovascular accidents, but some studies have also confirmed that allopurinol is a protective factor against stroke. To clarify whether there is a relevant causal relationship between allopurinol and cerebral infarction, we conducted a two-sample Mendelian randomization (MR) study.
Data on single nucleotide polymorphisms (SNPs) associated with allopurinol and genome-wide association studies of cerebral infarction were obtained from the genome-wide association study (GWAS) web site. Five basic MR analyses were performed using MR-Egger regression, weighted median (WM1), inverse variance weighting (IVW), weighted mode (WM2), and simple mode. Sensitivity analysis was subsequently performed to detect horizontal pleiotropy, heterogeneity, and potential outliers. The final analysis results were mainly based on the IVW estimates.
A total of 10 SNPs were used as instrumental variables (IVs). MR analysis [(IVW: odds ratio (OR) = 1.053, 95% confidence interval (CI): 1.019-1.088, = 0.002), (WM1: OR = 1.053, 95% CI: 1.009-1.098, = 0.017), (WM2: OR = 1.050, 95% CI: 1.008-1.095, = 0.044), (MR Egger: = 4.285, = 0.830)] showed a positive causal association between allopurinol and the risk of cerebral infarction. Sensitivity analysis such as horizontal pleiotropy and heterogeneity increased the reliability of this result.
The results of this study provide direct evidence that there is a causal relationship between allopurinol and cerebral infarction and that allopurinol may increase the risk of cerebral infarction.
既往研究报道别嘌醇使用不当可能增加脑血管意外风险，但也有研究证实别嘌醇是预防中风的保护因素。为明确别嘌醇与脑梗死之间是否存在相关因果关系，我们进行了一项两样本孟德尔随机化（MR）研究。
从全基因组关联研究（GWAS）网站获取与别嘌醇相关的单核苷酸多态性（SNP）数据以及脑梗死的全基因组关联研究数据。使用MR-Egger回归、加权中位数（WM1）、逆方差加权（IVW）、加权模式（WM2）和简单模式进行了五项基本的MR分析。随后进行敏感性分析以检测水平多效性、异质性和潜在异常值。最终分析结果主要基于IVW估计值。
共10个SNP用作工具变量（IV）。MR分析[（IVW：比值比（OR）=1.053，95%置信区间（CI）：1.019-1.088，P=0.002），（WM1：OR=1.053，95%CI：1.009-1.098，P=0.017），（WM2：OR=1.050，95%CI：1.008-1.095，P=0.044），（MR Egger：P=4.285，P=0.830）]显示别嘌醇与脑梗死风险之间存在正因果关联。水平多效性和异质性等敏感性分析提高了该结果的可靠性。
本研究结果提供了直接证据，表明别嘌醇与脑梗死之间存在因果关系，且别嘌醇可能增加脑梗死风险。
