Peripheral Vascular Disease Susceptibility Based on Diabetes Mellitus and rs17367504 Polymorphism of the MTHFR Gene

Yin-Tso Liu; Chuan-Chao Lin; Lee Wang; Oswald Ndi Nfor; Shu-Yi Hsu; Chia-Chi Lung; Disline Manli Tantoh; Horng-Rong Chang; Yung-Po Liaw

doi:10.2147/DMSO.S309242

Peripheral Vascular Disease Susceptibility Based on Diabetes Mellitus and rs17367504 Polymorphism of the MTHFR Gene

Diabetes Metab Syndr Obes. 2021 May 26:14:2381-2388. doi: 10.2147/DMSO.S309242. eCollection 2021.

Authors

Yin-Tso Liu^{1

2}, Chuan-Chao Lin^{3

4}, Lee Wang⁵, Oswald Ndi Nfor⁵, Shu-Yi Hsu⁵, Chia-Chi Lung⁵, Disline Manli Tantoh^{5

6}, Horng-Rong Chang^{1

7}, Yung-Po Liaw^{5

6}

Affiliations

¹ Institute of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan.
² Department of Cardiovascular Surgery, Asia University Hospital, Taichung, 40201, Taiwan.
³ Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan.
⁴ School of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan.
⁵ Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, 40201, Taiwan.
⁶ Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung City, 40201, Taiwan.
⁷ Division of Nephrology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan.

Abstract

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.

Keywords: atherosclerosis; genomics; peripheral vascular disease; type 2 diabetes.

Grants and funding

This study was supported by the Ministry of Science and Technology (MOST-109-2121-M-040-002).