The rs4712527 Polymorphism in the CDKAL1 Gene: A Protective Factor for Proliferative Diabetic Retinopathy Progress in Type 2 Diabetes

Diabetic retinopathy (DR) is one of the chronic retinal disorders linked to diabetes and remains the leading cause of blindness in working-age people. Many studies have demonstrated the existence of associations between type 2 diabetes mellitus (T2DM) and variants in the cyclin-dependent kinase 5 regulatory subunit–associated protein 1-like 1 (CDKAL1) gene. Here, we performed a case-control study in the CDKAL1 gene (rs4712527 polymorphism) to investigate the potential association between this single-nucleotide polymorphism (SNP) and DR risk. Two hundred thirty-one patients with T2DM (126 patients with proliferative diabetic retinopathy [PDR] and 105 patients without diabetic retinopathy [WDR]), who assisted at the Centro Privado de Ojos Romagosa, Fundación VER, were studied. An independent cohort of 98 patients (56 with PDR and 42 with WDR) from the Hospital Nacional de Clínicas was taken for replication. A complete ophthalmological examination included an external examination of the eye and adnexa, pupil responsiveness, and slit-lamp biomicroscopic examination. Genotyping of rs4712527 was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratio (OR) and 95% CI were calculated by unconditional logistic regression adjusted for diabetes duration, body mass index, insulin therapy, HbA1c, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and systolic and diastolic blood pressure. Analysis from the rs4712527 SNP in the Centro Privado de Ojos Romagosa, Fundación VER, cohort was found to be associated with decreased risk of PDR both before and after adjustment, under the codominant (adjusted OR = 0.16 [95% CI, 0.06-0.44]; P = 4e-04), dominant (adjusted OR = 0.17 [95% CI, 0.07-0.43]; P = 1e-04), overdominant (adjusted OR = 0.20 [95% CI, 0.08-0.52]; P = 5e-04), and log-additive (adjusted OR = 0.28 [95% CI, 0.13-0.59]; P = 4e-04) models. In the combined analysis including both cohorts, the rs4712527 was nominally involved as a protective factor in the development of DR. Our findings suggest that the rs4712527 in the CDKAL1 gene might be involved in the protection to develop PDR in T2DM