POS-324 ASSOCIATION OF VOLTAGE-DEPENDENT CALCIUM CHANNEL POLYMORPHISMS 1.3 WITH THE DEVELOPMENT OF DIABETIC NEPHROPATHY, DIABETIC RETINOPATHY AND DIABETIC NEUROPATHY

Abstract

One of the main characteristics of type 2 diabetes (T2D) is the lack of insulin secretion, this process is regulated by several proteins, within these are voltage-gated calcium channels, mainly CaV1.3 channels, whose single nucleotide polymorphisms (SNPs) have been associated in other populations with the presence of microvascular complications such as nephropathy, retinopathy and neuropathy in patients with T2D. Objective: To determine the association of the polymorphisms of the gene that codes for CaV1.3 with the risk of developing nephropathy, retinopathy and diabetic neuropathy. A case-control, comparative, observational, ambispective and cross-sectional study was carried out, in which men and women between 30 and 90 years of age participated, including patients with T2D according to the guidelines of the American Association. of Diabetes, with and without microvascular complications (nephropathy, retinopathy and neuropathy), treated in the outpatient clinic of the Internal Medicine Service, General Hospital “Dr. Manuel Gea González ”, from March to August 2020, from whom peripheral blood samples were taken for the extraction of genomic DNA by the phenol / chloroform method and subsequent genotyping, with the iPLEX Assay system that requires the design of specific oligonucleotides , amplification by polymerase chain reaction and finally detection of SNPs by mass spectrometry. A total of 200 patients participated in this study, 125 (62.5%) men and 75 (37.5%) women, within which 100 cases were divided into two groups (with a diagnosis of type 2 diabetes and the presence of nephropathy, retinopathy and neuropathy) and 100 controls (with a diagnosis of type 2 diabetes and absence of microvascular complications). A total of 4 polymorphisms of the CACNA1D gene were studied. Wild alleles were the most frequent in all groups. Within the polymorphisms analyzed in the binary logistic regression, rs9841978 GA (OR, 6.2; CI95%: 1.15-13.48, p = 0.03) and rs312486 CC (OR, 6.6; CI95%: 4.60-9.45, p = 0.002) with a Wald significance level of 4.51 and 9.51 respectively. In the multinomial logistic regression model, in diabetic retinopathy the variables were age (OR, 1.12; 95% CI: 1.03-1.22, p = 0.01), HT (OR, 5.92; 95% CI: 4.55-7.11, p = 0.002), rs9841978 GA (OR, 9.72; 95% CI: 3.62-10.72, p = 0.002) and rs312486 CC (OR, 1.09; 95% CI: 1.0004-1.19, p = 0.003). In diabetic nephropathy and neuropathy, the variable was the polymorphism rs9841978 GA, with OR, 12.55; CI95%: 4.80- 32.80, p = 0.03 and OR, 6.18; 95% CI: 2.90-13.16, p = 0.03, respectively. Our study demonstrated the association of well-established genetic variants of the polymorphisms of the CACNA1D gene with the presence of microvascular complications in patients with type 2 diabetes, showing that these SNPs, specifically rs9841978 GA and rs312486 CC, may represent important markers in the development of these complications of the disease, mainly nephropathy and retinopathy, and they are a predisposing factor due to the high frequency and strength of association observed in our study population, representing this the first study in Latin America. This suggests that our population is highly susceptible to developing not only T2D but also complications such as nephropathy and retinopathy that in the medium or long term could represent the cause of death in this sector when these SNPs are present.