Vitamin D, vitamin D receptor FokI polymorphism, and diabetic retinopathy: A case-control study in Kunming, China

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.