Liu YH, Guo C, Sun YQ, Li Q. Polymorphisms in HIF-1a gene are not associated with diabetic retinopathy in China. World J Diabetes 2021; 12(8): 1304-1311 [PMID: 34512895 DOI: 10.4239/wjd.v12.i8.1304]
Corresponding Author of This Article
Qiang Li, MD, PhD, Chief Physician, Department of Endocrinology, Shenzhen University General Hospital, No. 1098, Xueyuan Road, Nanshan District, Shenzhen 518055, Guangdong Province, China. qianglisz@163.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Aug 15, 2021; 12(8): 1304-1311 Published online Aug 15, 2021. doi: 10.4239/wjd.v12.i8.1304
Polymorphisms in HIF-1a gene are not associated with diabetic retinopathy in China
Yue-Hong Liu, Chang Guo, Yi-Qiong Sun, Qiang Li
Yue-Hong Liu, Department of Endocrinology, Hainan Cancer Hospital, Haikou 570312, Hainan Province, China
Chang Guo, Yi-Qiong Sun, Qiang Li, Department of Endocrinology, Shenzhen University General Hospital, Shenzhen 518055,Guangdong Province, China
Author contributions: Liu YH is responsible for implementation of the study; Guo C and Sun YQ are responsible for the collation of data and the formation of research reports; Li Q is responsible for the design of the project and the review of articles.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Review Committee of The Second Affiliated Hospital of Harbin Medical University.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no competing interests.
Data sharing statement: Participants gave informed consent for data sharing.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qiang Li, MD, PhD, Chief Physician, Department of Endocrinology, Shenzhen University General Hospital, No. 1098, Xueyuan Road, Nanshan District, Shenzhen 518055, Guangdong Province, China. qianglisz@163.com
Received: February 23, 2021 Peer-review started: February 23, 2021 First decision: March 30, 2021 Revised: April 9, 2021 Accepted: July 12, 2021 Article in press: July 12, 2021 Published online: August 15, 2021 Processing time: 167 Days and 0.9 Hours
Abstract
BACKGROUND
It has been reported that vascular endothelial growth factor (VEGF) is a susceptibility gene for both type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR). In response to hypoxia, VEGF mRNA levels are increased, which is mainly mediated by the binding of hypoxia-inducible factor-1 (HIF-1) and hypoxia response element upstream of the transcriptional start site of VEGF. Therefore, HIF-1a is supposed to be involved in pathology of DR.
AIM
To investigate whether the polymorphisms in HIF-1a gene are associated with DR.
METHODS
Two hundred and ninety-nine type 2 diabetic patients (128 males and 171 females) and 144 healthy volunteers were recruited. Mean age was 56.04 ± 21.05 years. According to the results of fundus fluorescein angiography and examination of ophthalmoscopy, patients were divided into two groups, DNR group (diabetes without retinopathy) and DR group (diabetes with retinopathy). There are 150 cases in DNR group and 149 cases in DR group. Two single nucleotide polymorphisms (SNP) of the HIF-1a gene were tested using matrix-assisted laser desorption/Ionization time of flight mass spectrometry. The frequency of genotypes and alleles, and odds ratio were measured.
RESULTS
The mean age of the cases with diabetes was 55.84 ± 3.66 years, the mean age of the cases with DR was 55.97 ± 4.66 years and that of controls was 56.32 ± 4.70 years. Two variations were found in 76 patients. Rs11549465 is the change of C-T base, rs11549467 is the change of G-A base. The rs11549467 G/A genotype was 5.33% in diabetes and 6.04% in DR patients, respectively. The rs11549465 C/T genotype was 10% and 12.75% in patients with diabetes and DR. The rs11549467 A allele frequencies and rs11549465 T frequencies was similar to that of controls. Paired SNP linkage disequilibrium analysis indicated that rs11549467 was in linkage disequilibrium with rs11549465. Haplotype association analysis denoted that the haplotype association exhibited similar distribution in the patients compared to the normal controls.
CONCLUSION
This study suggests that there is no relationship between the genetic variations of HIF1a and diabetes or DR.
Core Tip: Vascular endothelial growth factor (VEGF), a potent endothelial cell mitogen, plays a crucial role in neovascularization of proliferative diabetic retinopathy (DR). The human VEGF gene encoding VEGF was identified to be the first target genes of hypoxia-inducible factor-1 (HIF-1). Therefore, HIF-1a is supposed to be involved in pathology of DR. Here, we investigate whether the polymorphisms in HIF-1a gene are associated with DR.
