<i>TLR4</i> Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin Resistance in Obese Female Subjects

• Main Authors: Elham Sharif, Mariam Al-Wakeel, Afnan Mohamed, Abdelhamid kerkadi, Nasser Rizk
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Genes
• Subjects: <i>TLR4</i> polymorphism; haplotype; insulin resistance and obesity
• Online Access: https://www.mdpi.com/2073-4425/11/7/814

Background: Activation of Toll-like-receptor 4 (<i>TLR4</i>) causes chronic inflammation that can result in obesity and metabolic syndrome (MeS). Aim: This study aimed to investigate the role of <i>TLR4</i> polymorphisms of <i>TLR4</i>D299G/T399I, and its impact on protein expression of <i>TLR4</i> in obese female subjects. Methodology: 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; <i>n</i> = 69” and “non-obese; <i>n</i> = 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 <i>TLR4</i> polymorphisms of <i>TLR4</i>D299G (rs4986790) and <i>TLR4</i>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 <i>TLR4</i>. Results: The frequency distribution of the genotype revealed that homozygous AA is the most frequent among obese subjects (86.4%) for (<i>TLR4</i>D299G, A > G) and the homozygous CC genotype is the most frequent (92.4%) for (<i>TLR4</i>T399I, C > T). Haplotype analysis of <i>TLR4</i> 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; <i>p</i>-value = 0.016). The monocyte cell surface of <i>TLR4</i> was significantly higher by 1.3 folds in obese compared to non-obese subjects. Conclusions: <i>TLR4</i> D299G/T399I haplotype polymorphism is associated with an increased risk of insulin resistance with the upregulation of <i>TLR4</i> protein expression in obese subjects.