Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China.
Guangxi University of Traditional Chinese Medicine, Nanning, Guangxi 530001, China.
Pain Res Manag. 2024 Apr 9;2024:4564596. doi: 10.1155/2024/4564596. eCollection 2024.
Two-sample Mendelian randomization (MR) was conducted to assess the causal relationship between angina pectoris and gout. . Based on genome-wide association studies, single nucleotide polymorphisms (SNPs) that were closely associated with gout were selected from the UK Biobank-Neale Lab (ukb-a-107) as genetic instrumental variables. Considering that gout is characterized by elevated blood uric acid levels, SNPs related to blood uric acid levels were screened from BioBank Japan (bbj-a-57) as auxiliary gene instrumental variables. SNPs closely associated with angina pectoris onset were screened from the FINN dataset (finn-b-I9_ANGINA) as outcome variables. Two-sample MR was conducted, with inverse variance weighting (IVW) of the random effects model as the primary result, along with the weighted median method (WME) and the MR-Egger regression method. To further confirm the causal relationship between angina and gout incidence, a meta-analysis was conducted on the IVW results of the ukb-a-107 and bbj-a-57.
The odds ratios and 95% confidence intervals of the IVW, WME, and MR-Egger results of ukb-a-107 were (OR = 33.72; 95% CI: 2.07∼550.38), (OR = 57.94; 95% CI: 2.75∼1219.82), and (OR = 96.38; 95% CI: 0.6∼15556.93), respectively. The values of IVW and WME were 0.014 and 0.014 (both <0.05), respectively, indicating that the development of angina pectoris was significantly associated with the incidence of gout. The odds ratios and 95% confidence intervals of the IVW, WME, and MR-Egger about bbj-a-57 were (OR = 1.20; 95% CI: 1.07∼1.34), (OR = 1.19; 95% CI: 1.02∼1.38), and (OR = 1.30; 95% CI; 1.06∼1.60), respectively. The values of IVW, WME and MR-Egger were 0.001, 0.027 and 0.017 (all <0.05), respectively, indicating a significant correlation between angina and blood uric acid levels. Scatter plots of ukb-a-107 and bbj-a-57 showed that the causal association estimates of the IVW, MR-Egger, and weighted median methods were similar and that the MR results were accurate. Funnel plots and the MR-Egger intercept of ukb-a-107 and bbj-a-57 showed the absence of horizontal pleiotropy. The leave-out sensitivity analysis results of ukb-a-107 and bbj-a-57 are stable. The meta-analysis of IVW results for ukb-a-107 and bbj-a-57 showed (OR = 1.20; 95% CI: 1.07-1.34, =0.02), confirming that gout characterized by high blood uric acid levels significantly increases the risk of angina attacks.
This MR study found a clear causal relationship between angina pectoris and gout, which increases the risk of angina pectoris.
采用两样本孟德尔随机化（MR）方法评估心绞痛和痛风之间的因果关系。基于全基因组关联研究，从英国生物库-尼尔实验室（ukb-a-107）中选择与痛风密切相关的单核苷酸多态性（SNP）作为遗传工具变量。由于痛风的特征是血尿酸水平升高，因此从日本生物银行（bbj-a-57）中筛选与血尿酸水平相关的 SNP 作为辅助基因工具变量。从芬兰数据集（finn-b-I9_ANGINA）中筛选与心绞痛发作密切相关的 SNP 作为结果变量。采用逆方差加权（IVW）随机效应模型作为主要结果，结合加权中位数法（WME）和 MR-Egger 回归法进行两样本 MR 分析。为进一步确认心绞痛和痛风发病率之间的因果关系，对 ukb-a-107 和 bbj-a-57 的 IVW 结果进行了荟萃分析。
ukb-a-107 的 IVW、WME 和 MR-Egger 结果的优势比和 95%置信区间分别为（OR=33.72；95%CI：2.07∼550.38）、（OR=57.94；95%CI：2.75∼1219.82）和（OR=96.38；95%CI：0.6∼15556.93）。IVW 和 WME 的 值分别为 0.014 和 0.014（均<0.05），表明心绞痛的发生与痛风的发病率显著相关。bbj-a-57 的 IVW、WME 和 MR-Egger 的优势比和 95%置信区间分别为（OR=1.20；95%CI：1.07∼1.34）、（OR=1.19；95%CI：1.02∼1.38）和（OR=1.30；95%CI：1.06∼1.60）。IVW、WME 和 MR-Egger 的 值分别为 0.001、0.027 和 0.017（均<0.05），表明心绞痛与血尿酸水平之间存在显著相关性。ukb-a-107 和 bbj-a-57 的散点图表明，IVW、MR-Egger 和加权中位数方法的因果关联估计值相似，MR 结果准确。ukb-a-107 和 bbj-a-57 的漏斗图和 MR-Egger 截距表明不存在水平偏倚。ukb-a-107 和 bbj-a-57 的剔除敏感性分析结果稳定。ukb-a-107 和 bbj-a-57 的 IVW 结果荟萃分析显示（OR=1.20；95%CI：1.07-1.34，=0.02），证实血尿酸水平升高导致的痛风显著增加了心绞痛发作的风险。
本 MR 研究发现心绞痛和痛风之间存在明确的因果关系，痛风会增加心绞痛的发病风险。
