Research Paper|Volume 12, Issue 13|pp 12783—12798

Genetic association of hypoxia inducible factor 1-alpha (HIF1A) Pro582Ser polymorphism with risk of diabetes and diabetic complications

Huan Ren^1,^2,^3,⁴, Jian-Quan Luo⁵, Yong-Chao Gao^1,^2,^3,⁴, Man-Yun Chen^1,^2,^3,⁴, Xiao-Ping Chen^1,^2,^3,⁴, Hong-Hao Zhou^1,^2,^3,⁴, Ying Jiang⁶, Wei Zhang^1,^2,^3,⁴

¹Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P.R. China
²Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, P.R. China
³Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, P.R. China
⁴National Clinical Research Center for Geriatric Disorders, Changsha, P.R. China
⁵Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, P.R. China
⁶Department of Cardiothoracic Surgery, Xiangya Hospital, Central South University, Changsha, P.R. China

Received: January 13, 2020Accepted: April 17, 2020Published: July 13, 2020

https://doi.org/10.18632/aging.103213

Copyright © 2020 Ren et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Diabetes is an age-related chronic disease associated with a number of complications, emerging as one of the major causes of morbidity and mortality worldwide. Several studies indicated that hypoxia-inducible factor 1-alpha (HIF1A) genetic polymorphisms may be associated with diabetes and diabetic complications. However, this association remains ambiguous. Thus, we performed a meta-analysis to provide more precise conclusion on this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were applied to assess the strength of the relationships. There was a protective association between HIF1A Pro582Ser polymorphism and diabetes under the heterozygous genetic model (OR = 0.70, 95% CI = 0.55-0.91; P = 0.007). Similar associations were observed in diabetic complications risk under the allelic (OR = 0.69, 95% CI = 0.57-0.83; P < 0.001), homozygous (OR = 0.51, 95% CI = 0.30-0.87; P = 0.014), recessive (OR = 0.73, 95% CI = 0.59-0.90; P = 0.004) and dominant (OR = 0.40, 95% CI = 0.25-0.65; P < 0.001) genetic models. No effects of the HIF1A Ala588Thr polymorphism were found in risk of diabetes and diabetic complications. Taken together, these findings revealed the protective effect of HIF1A Pro582Ser polymorphism against diabetes and diabetic complications.