MTHFR基因多型性與糖尿病對周邊血管疾病的影響

研究目的：周邊血管疾病是會對生命安全造成威脅，常見的危險因子包括: 糖尿病、高血壓、高血脂、抽菸、和年紀大等。台灣少有針對周邊血管疾病基因的研究。本研究的目的是: 檢視第2型糖尿病和血壓有關的Methylenetetrahydrofolate reductase基因對周邊血管疾病的影響。研究方法及資料：本篇研究是利用台灣人體生物資料庫建立的研究族群，總共納入8992位研究個案，年齡介於30歲至70多歲之間，收案期間為2008年至2015年。運用多項式邏輯式回歸測試周邊血管疾病和rs17367504以及糖尿病間的關係，再以Axiom-Taiwan Biobank Array Plate 晶片來分析rs17367504變異體。研究結果：第2型糖尿病人(n=1294)中有158人(12.21%)有周邊血管疾病，第2型糖尿病和周邊血管疾病有相關，勝算比為1.52，95%信賴區間為1.21-1.91，P< 0.001；然而，第2型糖尿病和rs17367504無相關，在比較AG/GG和AA同型合子(homozygotes)的勝算比為0.96，95%信賴區間為0.76-1.21，P=0.728；第2型糖尿病和rs17367504對周邊血管疾病卻有交互影響(P=0.0076)；再細看分層分析，糖尿病人具AA同型合子者的勝算比為0.75(信賴區間為1.35-2.26；P<0.001)； 糖尿病人具AG+GG同型合子者的勝算比為0.94(信賴區間為0.56-1.58;P=0.811)。 結論：從台灣的人體生物資料庫中我們發現那些rs17367504變異體中有AA基因者的第2型糖尿病人會增加周邊血管疾病的風險。

Purpose: Peripheral vascular disease (PVD) is a life-threatening condition affecting the lower extremities. Common risk factors include type 2 diabetes (T2D), hypertension, dyslipidemia, smoking, and older age. There is a little-documented research on the genetic basis of the disease in Taiwan. We examined the impact of T2D and the blood pressure-associated rs17367504 variant of the Methylenetetrahydrofolate reductase (MTHFR) gene on PVD risk. Materials and Methods: In this population-based association study, we linked data from 8992 participants in Taiwan Biobank (TWB) to their medical records in the National Health Insurance Research Database (NHIRD). Participants were 30 to 70 years old at recruitment and included those assessed between 2008 and 2015. We tested for association of PVD with rs17367504 and T2D using multiple logistic regression models. The rs17367504 variant was assessed using the Axiom-Taiwan Biobank Array Plate (TWB chip: Affymetrix, Inc., Santa Clara, CA, USA). Results: Among cases with T2D (n = 1294), 158 (12.21%) were identified with PVD. T2D was associated with PVD (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.21–1.91; p<0.001) whereas rs17367504 variant was not (OR, 0.96; CI, 0.76–1.21; p = 0.728 in AG/ GG compared to AA homozygotes). However, T2D and rs17367504 had an interactive effect on PVD (p for interaction = 0.0076). Results from our stratified analyses displayed OR of 1.75 (CI, 1.35–2.26; p<0.001) in AA individuals with DM and 0.94 (CI, 0.56–1.58; p = 0.811) in AG+GG individuals with T2D. Using the AA genotype and no T2D as the reference group, the respective OR of PVD was 1.77 (CI, 1.38–2.28; p<0.001) in AA individuals with T2D; 1.18 (CI, 0.91–1.55; p = 0.215) in AG+GG individuals with no T2D, and 1.03 (CI, 0.66–1.60; p = 0.892) in AG+GG individuals with T2D . Conclusion: We found that type 2 diabetes was associated with increased risk of peripheral vascular disease, particularly in AA genotype carriers of the rs17367504 variant in Taiwan.