4.0 Article

The A allele of the rs759853 single nucleotide polymorphism in the AKR1B1 gene confers risk for diabetic kidney disease in patients with type 2 diabetes from a Brazilian population

Journal

ARCHIVES OF ENDOCRINOLOGY METABOLISM
Volume 66, Issue 1, Pages 12-18

Publisher

SBEM-SOC BRASIL ENDOCRINOLOGIA & METABOLOGIA
DOI: 10.20945/2359-3997000000432

Keywords

DNA polymorphism; diabetic kidney disease

Funding

  1. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
  2. Fundo de Incentivo a Pesquisa e Eventos (Fipe) at Hospital de Clinicas de Porto Alegre [2018-0472]
  3. Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (Fapergs) [Fapergs/CNPq Pronex 12/2014: 16-2551-0000476-5]
  4. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (Capes)
  5. CNPq
  6. Capes

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This study investigated the association between the rs759853 polymorphism in the AKR1B1 gene and diabetic kidney disease (DKD) in Brazilian patients with type 2 diabetes mellitus (T2DM). The results suggest that the A/A genotype of the rs759853 polymorphism is associated with an increased risk for DKD in this population.
Objective:The AKR1B1 gene encodes an enzyme that catalyzes the reduction of glucose into sorbitol. Chronic hyperglycemia in patients with diabetes mellitus (DM) leads to increased AKR1B1 affinity for glucose and, consequently, sorbitol accumulation. Elevated sorbitol increases oxidative stress, which is one of the main pathways related to chronic complications of diabetes, including diabetic kidney disease (DKD). Accordingly, some studies have suggested the rs759853 polymorphism in the AKR1B1 gene is associated with DKD; however, findings are still contradictory. The aim was to investigate the association of the rs759853 polymorphism in the AKR1B1 gene and DKD. Materials and methods: The sample comprised 695 patients with type 2 DM (T2DM) and DKD (cases) and 310 patients with T2DM of more than 10 years' duration, but no DKD (controls). The polymorphism was genotyped by real-time PCR. Results: Allelic and genotype frequencies of this polymorphism did not differ significantly between groups. However, the A/A genotype was associated with risk for DKD after adjustment for gender, triglycerides, BMI, presence of hypertension and diabetic retinopathy, and duration of DM, under both recessive (P = 0.048) and additive (P = 0.037) inheritance models. Conclusion: Our data suggest an association between the AKR1B1 rs759853A/A genotype and risk for DKD in Brazilians T2DM patients. Arch Endocrinol Metab. 2022;66(1):12-8

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