Facultad de Nutrición, Universidad Autónoma del Estado de Morelos, Río Iztacihuatl S/N. Col. Vista Hermosa, C.P. 62350, Mexico, Mexico.
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, C.P. 04510, Ciudad de México, Mexico.
Biochem Genet. 2021 Aug;59(4):940-965. doi: 10.1007/s10528-021-10047-w. Epub 2021 Feb 18.
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.
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.
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.
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.
慢性低度炎症与 2 型糖尿病(T2DM)的病因密切相关,而炎症细胞因子的表达可能受到位于 NFκβ、IL-1β、IL-6、TNFα 和 LPL 基因调节区域的多态性的调节。我们认为,研究与慢性炎症相关的基因多态性与 T2DM 或未控制的生化参数风险之间的关系尤为重要。
我们纳入了 199 名 T2DM 患者和 213 名非 T2DM 患者。采用限制性片段长度多态性(RFLP)分析评估多态性。
我们发现,在墨西哥人群中,NFκβ 的 del/del 基因型、IL-6 的-174 和-572 基因型、IL-1β 的 C/C 基因型、TNFα 的-308 和-238 基因型以及 LPL 的 T/T 基因型与 T2DM 及未控制的生化参数之间存在风险关联。在无糖尿病(对照组)患者中,我们发现 IL-6 的-572 多态性的 G/C 基因型与-597 多态性的 G/C 和 C/C 基因型与血糖水平>131mg/dL的风险之间存在关联。IL-6 基因的-174 多态性的 C/C 基因型与高甘油三酯水平相关,HbA1c 水平>5.8%与 TNFα-308 的 G/A 基因型相关。
在此,我们首次描述了 NFκβ、IL-6、TNFα、IL-1β 和 LPL 基因的多态性与 T2DM 风险和未控制的生化参数之间的关系。我们还表明,对于本研究纳入的人群,所研究基因的多态性具有累加效应,极大地增加了发生 T2DM 的风险。我们还表明,与慢性炎症相关的基因之间存在相互作用,影响 T2DM 的风险。