Department of Biomedical Science, Hallym University, Chuncheon, 200-702, Gangwon-do, Republic of Korea.
Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology, Gangneung, Republic of Korea.
Genes Genomics. 2019 May;41(5):537-545. doi: 10.1007/s13258-019-00791-0. Epub 2019 Feb 14.
Type 2 diabetes (T2D) is known as an inflammatory disease. NRF2 (Nuclear Factor Erythroid 2 Like2) encodes a transcription factor that binds to antioxidant response elements (AREs) and regulates the expression of genes involved in many antioxidant responses.
This study aimed to gain insight into individual anti-inflammatory activity to prevent T2D development in humans.
We performed a genome-wide association study (GWAS) to identify genetic variants influencing NRF2 expression in LCLs (lymphoblastoid cell lines) generated from 74 different individuals. Association analyses between T2D or its related traits and genetic risk score (GRS) calculated by combining genetic variants detected from GWAS for cellular NRF2 expression were performed using data from 8715 subjects. The T2D prediction model using GRS was evaluated by measuring the area under the curve (AUC) of the receiver operating characteristics (ROC) curve.
Our GWAS identified six genetic variants (SNP) showing suggestive evidence of associations with cellular NRF2 expression (P < 10). Logistic regression analysis demonstrated that GRS was associated with an increased risk of T2D (P value = 0.003, OR = 1.13). In addition, linear regression analyses showed positive associations between GRS and fasting glucose (P value = 0.028, β = 0.62), 2-h glucose (P value = 0.0004, β = 1.13) and HbA1C (P value = 0.033, β = 0.03). In the T2D prediction model using GRS, the AUC of the ROC curve was 0.69.
This study highlights genetic variants associated with cellular NRF2 expression and suggests that the GRS of NRF2 expression-associated variants is likely to be a useful indicator of T2D development in the human population.
2 型糖尿病（T2D）被认为是一种炎症性疾病。NRF2（Erythroid 2 样转录因子 2）编码一种转录因子，它与抗氧化反应元件（AREs）结合，调节参与许多抗氧化反应的基因的表达。
本研究旨在深入了解个体的抗炎活性，以预防人类 T2D 的发生。
我们进行了全基因组关联研究（GWAS），以确定影响 74 个不同个体的 LCL（淋巴母细胞系）中 NRF2 表达的遗传变异。使用来自 8715 名受试者的数据，对 T2D 或其相关特征与通过 GWAS 检测到的与细胞 NRF2 表达相关的遗传风险评分（GRS）之间的关联进行了分析。使用 GRS 的 T2D 预测模型通过测量接收者操作特征（ROC）曲线下的面积（AUC）来进行评估。
我们的 GWAS 确定了六个具有细胞 NRF2 表达关联的遗传变异（SNP）（P<10），具有提示性证据。逻辑回归分析表明，GRS 与 T2D 风险增加相关（P 值=0.003，OR=1.13）。此外，线性回归分析显示 GRS 与空腹血糖（P 值=0.028，β=0.62）、2 小时血糖（P 值=0.0004，β=1.13）和 HbA1C（P 值=0.033，β=0.03）呈正相关。在使用 GRS 的 T2D 预测模型中，ROC 曲线的 AUC 为 0.69。
本研究强调了与细胞 NRF2 表达相关的遗传变异，并表明 NRF2 表达相关变异的 GRS 可能是人类 T2D 发展的有用指标。
