NOS3 rs1799983 and rs2070744 polymorphisms and their association with advanced chronic kidney disease and coronary heart disease in Canarian population with type 2 diabetes

M Boronat; A Tugores; P Saavedra; P Garay; E Bosch; D Lorenzo; A Ibarra; C García-Cantón

doi:10.4183/aeb.2021.440

NOS3 rs1799983 and rs2070744 polymorphisms and their association with advanced chronic kidney disease and coronary heart disease in Canarian population with type 2 diabetes

Acta Endocrinol (Buchar). 2021 Oct-Dec;17(4):440-448. doi: 10.4183/aeb.2021.440.

Authors

M Boronat^{1

2}, A Tugores³, P Saavedra⁴, P Garay², E Bosch⁵, D Lorenzo⁶, A Ibarra², C García-Cantón⁵

Affiliations

¹ Instituto Universitario de Investigaciones Biomédicas y Sanitarias, University of Las Palmas de Gran Canaria, Faculty of Health Sciences, Spain.
² Section of Endocrinology and Nutrition, University of Las Palmas de Gran Canaria, Faculty of Health Sciences, Spain.
³ Research Unit, University of Las Palmas de Gran Canaria, Faculty of Health Sciences, Spain.
⁴ Mathematics Department - Complejo Hospitalario Materno-Insular, University of Las Palmas de Gran Canaria, Faculty of Health Sciences, Spain.
⁵ Service of Nephrology University of Las Palmas de Gran Canaria, Faculty of Health Sciences, Spain.
⁶ Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain.

Abstract

Context: Different polymorphisms of the endothelial nitric oxide synthase gene (NOS3) have been related to diabetic kidney disease.

Objective: To evaluate the association between advanced diabetic chronic kidney disease (ACKD) and the rs1799983 and rs2070744 poymorphisms of NOS3 in a population from the Gran Canaria island.

Design: Cross-sectional case-control study.

Subjects and methods: Polymorphisms were genotyped in 152 subjects with ACKD secondary to type 2 diabetes [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m²], 110 subjects with type 2 diabetes for 20 or more years since diagnosis without ACKD (eGFR ≥45 mL/min/1.73m² and albumin/creatinine ratio <300 mg/g and/or 24-h urinary albumin excretion <300 mg) and 292 healthy controls. Association between both polymorphisms and established coronary heart disease (CHD) was also analyzed in both groups with diabetes.

Results: A greater proportion of homozygous individuals for the risk allele C of rs2070744 was found among subjects with ACKD. Association between ACKD and rs2070744 was observed in a recessive genetic model, both for comparison to subjects with diabetes but no ACKD [OR 2.17 (95% CI: 1.17-4.00), p=0.014] and for comparison to healthy controls [OR 1.61 (1.03-2.52), p=0.036]. The frequency of the C allele was significantly higher among subjects with CHD, but only in the group with ACKD. No associations were found for rs1799983.

Conclusions: NOS3 rs2070744 is associated with ACKD in population with type 2 diabetes from Gran Canaria. A link between this genetic variant and CHD in Canarian subjects with type 2 diabetes could be restricted to cases with ACKD.

Keywords: NOS3; chronic kidney disease; coronary heart disease; diabetic nephropathy; endothelial nitric oxide synthase; type 2 diabetes.