Chen Zhimin, Wang Yujia, Xu Yanfang
Department of Nephrology, Blood Purification Research Center, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Medicine (Baltimore). 2024 Dec 6;103(49):e40827. doi: 10.1097/MD.0000000000040827.
Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of life-threatening autoimmune small vessel vasculitis and the prognosis depends heavily on whether a prompt diagnosis is achieved. Autoimmune thyroiditis is the most common autoimmune endocrine disease and could overlap with other autoimmune diseases. It remains elusive whether autoimmune thyroiditis affects the risk of AAV development. We performed a 2-sample Mendelian randomization analysis to explore the true association between autoimmune thyroiditis and microscopic polyangiitis (MPA), a subtype of AAV. Independent single-nucleotide polymorphisms associated with Hashimoto thyroiditis or Grave disease with genome-wide significance were selected as instrumental variables from large genome-wide association study. MPA genome-wide association study summary statistics were obtained from FinnGen consortium. The inverse-variance weighted method was conducted as the primary analysis for estimating the effect of the exposure on the outcome. Mendelian randomization-Egger and the weighted median method were used to confirm the results. We found a causal association between Hashimoto thyroiditis and MPA while no causal effect of Grave disease on MPA. This study contributed a genetic viewpoint to the understanding of the link between autoimmune thyroiditis and AAV.
抗中性粒细胞胞浆抗体相关性血管炎(AAV)是一组危及生命的自身免疫性小血管炎,其预后在很大程度上取决于能否及时诊断。自身免疫性甲状腺炎是最常见的自身免疫性内分泌疾病,可能与其他自身免疫性疾病重叠。自身免疫性甲状腺炎是否会影响AAV发生的风险仍不清楚。我们进行了一项两样本孟德尔随机化分析,以探讨自身免疫性甲状腺炎与AAV的一种亚型——显微镜下多血管炎(MPA)之间的真实关联。从大型全基因组关联研究中选择与具有全基因组意义的桥本甲状腺炎或格雷夫斯病相关的独立单核苷酸多态性作为工具变量。MPA全基因组关联研究汇总统计数据来自芬兰基因组联盟。采用逆方差加权法作为估计暴露对结局影响的主要分析方法。采用孟德尔随机化-伊格法和加权中位数法对结果进行验证。我们发现桥本甲状腺炎与MPA之间存在因果关联,而格雷夫斯病对MPA没有因果效应。这项研究为理解自身免疫性甲状腺炎与AAV之间的联系提供了一个遗传学视角。