Identifying the Genetic Associations Between Diabetes Mellitus and the Risk of Vitiligo.

IF 1.9 4区医学 Q3 DERMATOLOGY Clinical, Cosmetic and Investigational Dermatology Pub Date : 2024-10-13 eCollection Date: 2024-01-01 DOI:10.2147/CCID.S480199

Lingyun Zhao, Meng Hu, Li Li

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Abstract

Purpose: While increasing observational studies have suggested an association between diabetes mellitus (DM) and vitiligo, the causal relationship and possible mechanism remain unclear.

Methods: 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.

Results: IVW method showed a significant genetic causal association between DM and vitiligo (OR = 1.20, 95% CI: 1.08-1.33, P_IVW = 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_IVW = 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.

Conclusion: 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.

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确定糖尿病与白癜风风险之间的遗传关联。

目的：尽管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，但其因果关系和可能的机制仍不清楚：方法：利用公开的全基因组关联研究（GWAS）进行双向双样本孟德尔随机化（MR）分析。糖尿病和白癜风的 GWAS 数据分别来自英国生物库联盟（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），用于初步分析。主要分析方法为反方差加权法（IVW）。此外，还采用了多项敏感性分析来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生成效应的可能机制，利用 DAVID 和 STRING 数据库进行了富集分析：IVW方法显示，DM与白癜风之间存在明显的遗传因果关系（OR = 1.20，95% CI：1.08-1.33，PIVW = 0.0009）。糖尿病亚型分析表明，T2D（2 型糖尿病）与白癜风风险增加有关（OR = 1.13，95% CI：1.00-1.27，PIVW = 0.0432）。敏感性分析进一步证实了结果的稳健性。富集分析显示，糖尿病对白癜风的遗传诱导作用主要涉及胰腺分泌和蛋白质消化吸收途径：我们的研究结果提供了遗传学证据，证明在欧洲人群中，T2D 与白癜风风险升高之间存在显著关联。这一结果可以解释为什么在观察性研究中经常出现 T2D 和白癜风同时存在的现象，并强调了对确诊为 T2D 患者的白癜风进行警惕性监测和临床评估的重要性。糖尿病引起的糖脂代谢异常和白癜风的原发性营养吸收障碍可能是这种关联背后的潜在机制。

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来源期刊

Clinical, Cosmetic and Investigational Dermatology Medicine-Dermatology

CiteScore

2.80

自引率

4.30%

发文量

353

审稿时长

16 weeks

期刊介绍： Clinical, Cosmetic and Investigational Dermatology is an international, peer-reviewed, open access journal that focuses on the latest clinical and experimental research in all aspects of skin disease and cosmetic interventions. Normal and pathological processes in skin development and aging, their modification and treatment, as well as basic research into histology of dermal and dermal structures that provide clinical insights and potential treatment options are key topics for the journal. Patient satisfaction, preference, quality of life, compliance, persistence and their role in developing new management options to optimize outcomes for target conditions constitute major areas of interest. The journal is characterized by the rapid reporting of clinical studies, reviews and original research in skin research and skin care. All areas of dermatology will be covered; contributions will be welcomed from all clinicians and basic science researchers globally.