Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study.
Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study.
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DOI：
10.1186/s12933-023-02086-x
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发表时间：
2023-12-20
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
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原发性醛固酮增多症(PA)是一种自主分泌醛固酮的肾上腺疾病，可促进动脉损伤。我们的目的是探索PA是否与下肢动脉疾病(LEAD)有因果关系。我们包括来自英国生物库的39,713名糖尿病患者和419,312名非糖尿病参与者。我们根据先前的全基因组关联研究得出了PA的多基因风险评分(PRS)。结果包括铅和铅相关的坏疽或截肢。我们对PA和预后进行了两样本孟德尔随机化分析，以探索它们之间的潜在因果关系。在整个人群中，PA PR较高的个体患铅的风险增加。在糖尿病患者中，与PA PRS前三分位数的受试者相比，第三个三分位数的受试者患铅的风险是前者的1.24倍(OR 1.24，95%CI 1.03-1.49)，患坏疽的风险是后者的2.09倍(OR 2.09，95%CI为1.27-3.44)，截肢风险是后者的1.72倍(OR 1.72，95%CI 1.10-2.67)。在没有糖尿病的受试者中，PA-PRS与铅、坏疽或截肢没有显著关联。两样本孟德尔随机化分析表明，PA的遗传预测因素与铅和坏疽的风险显著相关(铅的逆方差加权OR1.20[95%CI 1.08-1.34]，坏疽的1.48[95%CI 1.28-1.70])，没有明显的异质性或方向性多效性的证据。原发性醛固酮增多症在遗传和因果关系上与铅和坏疽的风险有关，特别是在糖尿病患者中。以自主的醛固酮分泌为靶点可能会阻止进展。网上版载有补充材料，可在10.1186/s12933-023-02086-x查阅。
Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD). We included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship. In whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03–1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27–3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10–2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08–1.34]) for LEAD, 1.48 [95% CI 1.28–1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy. Primary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression. The online version contains supplementary material available at 10.1186/s12933-023-02086-x.
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影响因子：
16.6
作者：
通讯作者：
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与肾素非依赖性醛固酮增多症和肾素依赖性醛固酮增多症相关的高血压心血管风险增加：一项合作研究
影响因子：
5.4
作者：
Hu, Jinbo;Shen, Hang;Huo, Peiqi;Yang, Jun;Fuller, Peter J.;Wang, Kanran;Yang, Yi;Ma, Linqiang;Cheng, Qingfeng;Gong, Lilin;He, Wenwen;Luo, Ting;Mei, Mei;Wang, Yue;Du, Zhipeng;Luo, Rong;Cai, Jun;Li, Qifu;Song, Ying;Yang, Shumin
通讯作者：
Yang, Shumin
内皮盐皮质激素受体激活介导饮食引起的肥胖中的内皮功能障碍。
影响因子：
39.3
作者：
Schäfer N;Lohmann C;Winnik S;van Tits LJ;Miranda MX;Vergopoulos A;Ruschitzka F;Nussberger J;Berger S;Lüscher TF;Verrey F;Matter CM
通讯作者：
Matter CM
DOI：
10.1097/ede.0000000000000559
发表时间：
2017-01
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Burgess S;Bowden J;Fall T;Ingelsson E;Thompson SG
通讯作者：
Thompson SG
影响因子：
5.8
作者：
Funder, John W.;Carey, Robert M.;Young, William F., Jr.
通讯作者：
Young, William F., Jr.