Liu ZH, Ran ZQ, Yang R, Chen LX, Wang ZZ, Li YY, Han R. Vitamin D, vitamin D receptor FokI polymorphism, and diabetic retinopathy: A case-control study in Kunming, China. World J Diabetes 2026; 17(5): 118141 [DOI: 10.4239/wjd.v17.i5.118141]
Corresponding Author of This Article
Rui Han, MD, Professor, Department of International Medicine, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming 650032, Yunnan Province, China. gjyxbylyh@163.com
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Genetics & Heredity
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Case Control Study
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May 15, 2026 (publication date) through May 14, 2026
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World Journal of Diabetes
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1948-9358
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Liu ZH, Ran ZQ, Yang R, Chen LX, Wang ZZ, Li YY, Han R. Vitamin D, vitamin D receptor FokI polymorphism, and diabetic retinopathy: A case-control study in Kunming, China. World J Diabetes 2026; 17(5): 118141 [DOI: 10.4239/wjd.v17.i5.118141]
World J Diabetes. May 15, 2026; 17(5): 118141 Published online May 15, 2026. doi: 10.4239/wjd.v17.i5.118141
Vitamin D, vitamin D receptor FokI polymorphism, and diabetic retinopathy: A case-control study in Kunming, China
Ze-Hui Liu, Zhen-Qin Ran, Rong Yang, Li-Xin Chen, Zi-Zhou Wang, Yi-Yu Li, Rui Han
Ze-Hui Liu, Zhen-Qin Ran, Rong Yang, Li-Xin Chen, Zi-Zhou Wang, Rui Han, Department of International Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
Yi-Yu Li, School of Economics, Yunnan University, Kunming 650500, Yunnan Province, China
Co-first authors: Ze-Hui Liu and Zhen-Qin Ran.
Author contributions: Liu ZH and Ran ZQ contributed equally to this work. Both authors contributed to methodology, formal analysis, data extraction, follow-up, writing, reviewing, and editing as co-first authors; Yang R and Chen LX were involved in the supervision and software; Wang ZZ and Li YY contributed to data curation; Han R contributed to the analysis and provided guidance for the research; all authors have read and approved the final manuscript.
Supported by Yunnan Province International Joint Laboratory for Innovation and Application of Key Technologies in the Diagnosis and Treatment of Diabetes Mellitus and Chronic Complications, No. 202503AP140036; Yunnan Provincial Science and Technology Department-Kunming Medical University Basic Research Program, No. 202501AY070001-009; and Famous Doctor Special Project of Yunnan Xingdian Talent Support Program, No. XDYC-MY-2022-0004.
Institutional review board statement: This study was approved by the Institutional Review Board of the First Affiliated Hospital of Kunming Medical University.
Informed consent statement: All participants provided informed consent.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
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.
Data sharing statement: The authors confirm that the data supporting the findings of this study are available within the article, no additional data are available.
Corresponding author: Rui Han, MD, Professor, Department of International Medicine, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming 650032, Yunnan Province, China. gjyxbylyh@163.com
Received: December 25, 2025 Revised: February 24, 2026 Accepted: April 3, 2026 Published online: May 15, 2026 Processing time: 137 Days and 21.6 Hours
Abstract
BACKGROUND
Diabetic retinopathy (DR) is a prevalent and vision-threatening microvascular complication of type 2 diabetes mellitus (T2DM). Although traditional risk factors for DR are well established, the roles of vitamin D (VD) and genetic variations, particularly the VD receptor (VDR) FokI polymorphism (rs2228570), remain not fully elucidated in the pathogenesis of DR and are under active investigation. VD exerts anti-inflammatory, anti-oxidative, and anti-angiogenic effects that are crucial for retinal microvascular homeostasis. We hypothesized that serum VD levels and the VDR FokI polymorphism are associated with susceptibility to DR.
AIM
To investigate associations of serum VD levels and the VDR FokI polymorphism with the risk of DR in T2DM patients in Kunming, China.
METHODS
This case-control study was conducted at the First Affiliated Hospital of Kunming Medical University. Participants were recruited and categorized into three groups: (1) 115 patients with DR; (2) 130 T2DM patients without retinopathy; and (3) 58 healthy controls. Serum 25-hydroxyvitamin D levels were measured by chemiluminescence immunoassay. VDR FokI (rs2228570) genotyping was performed using Sanger sequencing.
RESULTS
The prevalence of VD deficiency (VDD) was significantly higher in the DR group (54.78%) compared with the T2DM (31.54%) and control groups (20.69%). VDD was significantly associated with an increased risk of DR relative to T2DM patients and healthy controls [odds ratio (OR) = 3.09, 95%CI: 1.90-5.01, P < 0.001]. Genetic analysis revealed that both the FokI ff genotype (OR = 2.36; 95%CI: 1.27-4.39; P = 0.007) and f allele (OR = 1.67; 95%CI: 1.18-2.36; P = 0.004) were substantially more prevalent in DR patients than in non-retinopathy T2DM patients and controls, suggesting that these genetic variants are associated with the development of DR.
CONCLUSION
VDD and the VDR FokI ff genotype are independent risk factors for DR in T2DM patients in Kunming, China. Their combined assessment may aid in DR risk stratification and early intervention.
Core Tip: This study identified vitamin D (VD) deficiency and VD receptor FokI ff genotype as independent risk factors for diabetic retinopathy in type 2 diabetes mellitus patients. Assessment of VD deficiency status and VD receptor FokI genotyping may facilitate diabetic retinopathy risk stratification and early intervention.
