Genetic interaction in the association between oxidative stress and diabetes in the Spanish population

Autores de INCLIVA

• Rebeca Melero Valverde

  Autor

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  María Elena Quiroz Rodríguez

  Autor

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  Francisco Lara Hernández

  Autor

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  Josep Redón Mas

  Autor

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  Felipe Javier Chaves Martínez

  Autor

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  Ana Barbara García García

  Autor

Participantes ajenos a INCLIVA

• Saez, Guillermo
• Briongos-Figuero, Laisa S
• Abadia-Otero, Jessica
• Martin-Escudero, Juan Carlos
• Ayala, Guillermo

Grupos y Plataformas de I+D+i

• Grupo de Estudio de Riesgo Cardiometabólico y Renal

  

  Established Researcher

  Raquel Cortés Vergaz

• Unidad de Genómica y Diabetes

  

  Established Researcher

  Felipe Javier Chaves Martínez

Abstract

Oxidative stress (OS) is a relevant intermediate mechanism involved in Type 2 Diabetes Mellitus (T2D) development. To date, the interaction between OS parameters and variations in genes related to T2D has not been analyzed. Aims: To study the genetic interaction of genes potentially related to OS levels (redox homeostasis, reninangiotensin-aldosterone system, endoplasmic stress response, dyslipidemia, obesity and metal transport) and OS and T2D risk in a general population from Spain (the Hortega Study) in relation to the risk of suffering from T2D. Materials and methods: One thousand five hundred and two adults from the University Hospital Rio Hortega area were studied and 900 single nucleotide polymorphisms (SNPs) from 272 candidate genes were analyzed. Results: There were no differences in OS levels between cases and controls. Some polymorphisms were associated with T2D and with OS levels. Significant interactions were observed between OS levels and two polymorphisms in relation to T2D presence: rs196904 (ERN1 gene) and rs2410718 (COX7C gene); and between OS levels and haplotypes of the genes: SP2, HFF1A, ILI8R1, EIF2AK2, TXNRD2, PPARA, NDUFS2 and ERN1. Conclusions: Our results indicate that genetic variations of the studied genes are associated with OS levels and that their interaction with OS parameters may contribute to the risk of developing T2D in the Spanish general population. These data support the importance of analyzing the influence of OS levels and their interaction with genetic variations in order to establish their real impact in T2D risk. Further studies are required to identify the real relevance of interactions between genetic variations and OS levels and the mechanisms involved in them.

Copyright © 2023 Elsevier Inc. All rights reserved.

Keywords

• Type 2 diabetes mellitus; Oxidative stress; SNP; Haplotype; Logistic regression model; Endoplasmic reticulum stress