Association of NFκβ, TNFα, IL-6, IL-1β, and LPL Polymorphisms with Type 2 Diabetes Mellitus and Biochemical Parameters in a Mexican Population

• Published in: Biochemical genetics Vol. 59; no. 4; pp. 940 - 965
• Main Authors: Martínez-Ramírez, O. C., Salazar-Piña, D. A., de Lorena, Ramos-García M., Castro-Hernández, C., Casas-Ávila, L., Portillo-Jacobo, J. A., Rubio, J.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2021; Springer Nature B.V
• Subjects: additive effect; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cytokines; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diagnosis; Etiology; Gene polymorphism; Genes; genotype; Genotype & phenotype; Genotypes; glucose; Human Genetics; IL-1β; Inflammation; Interleukin 6; Medical Microbiology; noninsulin-dependent diabetes mellitus; Original Article; Parameters; Polymorphism; Population; Population studies; Regulatory sequences; Restriction fragment length polymorphism; Risk; triacylglycerols; Triglycerides; Tumor necrosis factor-α; Zoology; T2DM; LPL; Inflammation; Interleukins; Polymorphisms
• ISSN: 0006-2928; 1573-4927; 1573-4927
• DOI: 10.1007/s10528-021-10047-w

Chronic low-grade inflammation is strongly related to the etiology of diabetes mellitus type 2 (T2DM), and the expression of inflammatory cytokines may be modulated by polymorphisms located in the regulatory regions of the NFκβ, IL-1β, IL-6, TNFα, and LPL genes. We considered it particularly important to investigate the relationship of gene polymorphisms involved in chronic inflammation with the risk of T2DM or uncontrolled biochemical parameters. Methods: We included 199 individuals with a T2DM diagnosis and 213 individuals without a T2DM diagnosis. Restriction fragment length polymorphism (RFLP) analyses were used to assess polymorphisms. Results: We found a risk association between T2DM and uncontrolled biochemical parameters in a Mexican population for the genotypes del/del of NFκβ , -174 and -572 of IL-6 , C/C of IL-1β, - 308 and -238 of TNFα, and T/T of LPL . In subjects without diabetes (controls), we found an association between the G/C genotype of the -572 polymorphism and the G/C and C/C genotypes of the -597 polymorphism of IL-6 with the risk of glucose levels > 131 mg/dL. Genotype C/C of polymorphism -174 of the IL-6 gene was associated with high triglyceride levels, and levels > 5.8% of HbA1c were associated with the G/A genotype of TNFα -308. Conclusion: Here, we describe for the first time the relationship of T2DM risk and uncontrolled biochemical parameters with polymorphisms in the NFκβ, IL-6 , TNFα , IL-1β, and LPL genes in a Mexican population. We also showed that for the population included in this study, there is an additive effect of the polymorphisms of the studied genes that considerably increases the risk of developing T2DM.We also showed that there are interactions between genes related to chronic inflammation that affect the risk of T2DM.