%0 Journal Article
%T The rs4712527 Polymorphism in the CDKAL1 Gene: A Protective Factor for Proliferative Diabetic Retinopathy Progress in Type 2 Diabetes
%A Ana L. Gramajo
%A Ayl¨¦n Sein
%A Claudio P. Ju¨¢rez
%A Dante M. Beltramo
%A Emilio Alcoba
%A Jos¨¦ D. Luna
%A N¨¦stor W. Soria
%A Pablo Yang
%J Journal of VitreoRetinal Diseases
%@ 2474-1272
%D 2018
%R 10.1177/2474126418777405
%X 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¨Cassociated 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, Fundaci¨®n VER, were studied. An independent cohort of 98 patients (56 with PDR and 42 with WDR) from the Hospital Nacional de Cl¨ªnicas 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, Fundaci¨®n 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
%K CDKAL1 gene
%K polymorphism
%K rs4712527
%K diabetic retinopathy
%K type 2 diabetes
%U https://journals.sagepub.com/doi/full/10.1177/2474126418777405