Biomedical Sciences Department, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar.
Human Nutrition Department, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar.
Genes (Basel). 2020 Jul 17;11(7):814. doi: 10.3390/genes11070814.
Activation of Toll-like-receptor 4 () causes chronic inflammation that can result in obesity and metabolic syndrome (MeS).
This study aimed to investigate the role of polymorphisms of D299G/T399I, and its impact on protein expression of in obese female subjects.
A prospective cross-sectional association study was performed on Arab female subjects from Qatar University. The subjects were categorized according to BMI classifications into two groups: "obese; = 69" and "non-obese; = 136". Anthropometric measurements, weight (kg), height (m) and waist circumference (WC) were evaluated, and the body mass index (BMI) was calculated. Fasting blood samples were collected, and assessment of glucose, lipid profile, C-reactive protein (CRP), leptin, IL-6 and insulin was performed. Insulin resistance was computed using HOMA-IR. Genotyping of the polymorphisms of D299G (rs4986790) and T399I (rs4986791) was performed by the 5' nuclease assay by TaqMan MGB probe. Flow cytometry was used to evaluate the monocyte cell surface expression of .
The frequency distribution of the genotype revealed that homozygous AA is the most frequent among obese subjects (86.4%) for (D299G, A > G) and the homozygous CC genotype is the most frequent (92.4%) for (T399I, C > T). Haplotype analysis of D299G/T399I showed that GT carriers had a significant association with increased probability of insulin resistance (odds ratio = 4.73; 95% CI 1.19-18.90; -value = 0.016). The monocyte cell surface of was significantly higher by 1.3 folds in obese compared to non-obese subjects.
D299G/T399I haplotype polymorphism is associated with an increased risk of insulin resistance with the upregulation of protein expression in obese subjects.
Toll 样受体 4（）的激活会导致慢性炎症，从而导致肥胖和代谢综合征（MeS）。
本研究旨在探讨 D299G/T399I 多态性及其对肥胖女性受试者中蛋白表达的影响。
对来自卡塔尔大学的阿拉伯女性进行了前瞻性横断面关联研究。根据 BMI 分类，将受试者分为两组：“肥胖；n=69”和“非肥胖；n=136”。评估了体重（kg）、身高（m）和腰围（WC）等人体测量指标，计算了体重指数（BMI）。采集空腹血样，检测血糖、血脂谱、C 反应蛋白（CRP）、瘦素、白细胞介素 6（IL-6）和胰岛素。使用 HOMA-IR 计算胰岛素抵抗。通过 TaqMan MGB 探针 5' 核酸酶检测法对 D299G（rs4986790）和 T399I（rs4986791）的多态性进行基因分型。使用流式细胞术评估单核细胞表面的表达。
基因型的频率分布显示，肥胖组（D299G，A > G）中纯合 AA 最常见（86.4%），（T399I，C > T）中纯合 CC 最常见（92.4%）。D299G/T399I 单体型分析显示，GT 携带者发生胰岛素抵抗的概率显著增加（比值比=4.73；95%CI 1.19-18.90；-值=0.016）。与非肥胖组相比，肥胖组的单核细胞表面增加了 1.3 倍。
D299G/T399I 单体型多态性与肥胖患者中胰岛素抵抗风险增加相关，同时伴有蛋白表达上调。
