Zhao Lingyun, Hu Meng, Li Li
Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Clin Cosmet Investig Dermatol. 2024 Oct 13;17:2261-2271. doi: 10.2147/CCID.S480199. eCollection 2024.
While increasing observational studies have suggested an association between diabetes mellitus (DM) and vitiligo, the causal relationship and possible mechanism remain unclear.
Publicly accessible genome-wide association study (GWAS) was utilized to conduct a bidirectional two-sample Mendelian randomization (MR) analysis. GWAS data for diabetes and vitiligo were obtained from the UK Biobank Consortium (20203 cases and 388756 controls) and the current GWAS data with largest cases (GCST004785, 4680 cases and 39586 controls) for preliminary analysis, respectively. Inverse variance weighting (IVW) was used as the main analysis method. Several sensitivity analyses were utilized to test the pleiotropy or heterogeneity. To explore the possible mechanism of gene-generating effects represented by the final instrumental variables in the analysis, enrichment analysis was conducted using the DAVID and STRING database.
IVW method showed a significant genetic causal association between DM and vitiligo (OR = 1.20, 95% CI: 1.08-1.33, P = 0.0009). Diabetes subtype analysis showed that T2D (type 2 diabetes) were associated with an increased risk of vitiligo (OR = 1.13, 95% CI: 1.00-1.27, P = 0.0432). Sensitivity analysis further confirmed the robustness of the results. The enrichment analysis revealed that the genetic inducing effects of diabetes mellitus on vitiligo were primarily about pancreatic secretion and protein digestion and absorption pathway.
Our findings provide genetic evidence that there is a notable association between T2D and an elevated risk of vitiligo in European populations. This result may explain why the co-presentation of T2D and vitiligo is often seen in observational studies, and emphasize the significance of vigilant monitoring and clinical evaluations for vitiligo in individuals diagnosed with T2D. The aberrant glucose and lipid metabolism and the primary nutrient absorption disorder of vitiligo brought on by diabetes may be the potential mechanisms behind this association.
虽然越来越多的观察性研究表明糖尿病（DM）与白癜风之间存在关联，但其因果关系和潜在机制仍不清楚。
利用公开可用的全基因组关联研究（GWAS）进行双向两样本孟德尔随机化（MR）分析。糖尿病和白癜风的GWAS数据分别来自英国生物银行联盟（20203例病例和388756例对照）和目前病例数最多的GWAS数据（GCST004785，4680例病例和39586例对照）进行初步分析。采用逆方差加权（IVW）作为主要分析方法。进行了多项敏感性分析以检验多效性或异质性。为了探索分析中最终工具变量所代表的基因产生效应的可能机制，使用DAVID和STRING数据库进行了富集分析。
IVW方法显示DM与白癜风之间存在显著的遗传因果关联（OR = 1.20，95%CI：1.08 - 1.33，P = 0.0009）。糖尿病亚型分析表明，2型糖尿病（T2D）与白癜风风险增加相关（OR = 1.13，95%CI：1.00 - 1.27，P = 0.0432）。敏感性分析进一步证实了结果的稳健性。富集分析表明，糖尿病对白癜风的遗传诱导效应主要涉及胰腺分泌以及蛋白质消化和吸收途径。
我们的研究结果提供了遗传证据，表明在欧洲人群中T2D与白癜风风险升高之间存在显著关联。这一结果可能解释了为什么在观察性研究中经常看到T2D和白癜风同时出现，并强调了对诊断为T2D的个体进行白癜风警惕性监测和临床评估的重要性。糖尿病导致的白癜风患者异常的糖脂代谢和主要营养物质吸收障碍可能是这种关联背后的潜在机制。
