Type 2 diabetes mellitus (T2DM) accompanied by hyperlipidemia confers higher risk for diabetes as well as cardiovascular diseases. NF-κB is actively involved in generating low-grade inflammation and oxidative stress triggering the development of diabetic complications. In this study, we have attempted to investigate the association between NF-κB1 functional promoter polymorphism-94 ATTG insertion/deletion (rs28362491) with inflammatory markers in developing diabetes-linked dyslipidemia. We performed a case–control study in a total of 401 individuals belonging to three categories such as Type 2 diabetes with dyslipidemia, Type 2 diabetes without dyslipidemia, and normal healthy controls. Experiments were carried out using genotyping, real-time PCR, and western blot. Pearson’s correlation, analysis of variance, and logistic regression were utilized for statistical analysis. As per genetic association conducted in this study the SNP rs28362491 showed significant allelic and genotypic associations (Allelic: OR = 1.374, CI 0.9797–1.927, p = 0.003, and Genotypic in dominant model: OR = 1.77, CI 1.04–2.99, p = 0.002) with the risk of diabetes and associated dyslipidemia. The -94 ATTG insertion/insertion (ins/ins) genotype was associated with significantly increased level of serum TNF-α (p = 0.002), serum IL-6 (p = 0.067) in diabetes-induced dyslipidemia. Multiple linear regression analysis identifies independent correlation of Total cholesterol, HDL, LDL, TNF-α, and rs28362491 ATTG ins/ins with triglyceride in diabetic dyslipidemic condition. T2DM with dyslipidemia having ins/ins genotype showed significant increased expression of pro-inflammatory cytokines such as TNF-α, IL-6, and activation of NF-κB. Our study reports that individuals with ATTG insertion allele and ATTG ins/ins genotype at NF-κB1 promoter regulatory gene predicts the risk and severity of T2DM-linked dyslipidemia.

伴有高脂血症的 2 型糖尿病 (T2DM) 会增加患糖尿病和心血管疾病的风险。NF-κB 积极参与产生引发糖尿病并发症的低度炎症和氧化应激。在这项研究中，我们试图研究 NF-κB1 功能启动子多态性-94 ATTG 插入/缺失 (rs28362491) 与糖尿病相关血脂异常的炎症标志物之间的关联。我们在总共 401 名个体中进行了病例对照研究，这些个体属于三类，例如 2 型糖尿病合并血脂异常、2 型糖尿病无血脂异常和正常健康对照。使用基因分型、实时 PCR 和蛋白质印迹法进行实验。皮尔逊相关性，方差分析，和逻辑回归用于统计分析。根据本研究中进行的遗传关联，SNP rs28362491 显示出显着的等位基因和基因型关联（等位基因：OR = 1.374，CI 0.9797–1.927，p  = 0.003，显性模型中的基因型：OR = 1.77，CI 1.04–2.99，p  = 0.002）与糖尿病和相关血脂异常的风险。-94 ATTG 插入/插入 (ins/ins) 基因型与血清 TNF-α ( p  = 0.002)、血清 IL-6 ( p = 0.067) 在糖尿病引起的血脂异常中。多元线性回归分析确定总胆固醇、HDL、LDL、TNF-α 和 rs28362491 ATTG ins/ins 与糖尿病血脂异常状况中的甘油三酯的独立相关性。具有 ins/ins 基因型血脂异常的 T2DM 显示促炎细胞因子（如 TNF-α、IL-6 和 NF-κB 的激活）的表达显着增加。我们的研究报告称，在 NF-κB1 启动子调控基因上具有 ATTG 插入等位基因和 ATTG ins/ins 基因型的个体可预测 T2DM 相关血脂异常的风险和严重程度。