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

BACKGROUND: Activation of Toll-like-receptor 4 (TLR4) causes chronic inflammation that can result in obesity and metabolic syndrome (MeS). AIM: This study aimed to investigate the role of TLR4 polymorphisms of TLR4D299G/T399I, and its impact on protein expression of TLR4 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; n = 69" and "non-obese; n = 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 TLR4 polymorphisms of TLR4D299G (rs4986790) and TLR4T399I (rs4986791) was performed by the 5' nuclease assay by TaqMan MGB probe. Flow cytometry was used to evaluate the monocyte cell surface expression of TLR4. RESULTS: The frequency distribution of the genotype revealed that homozygous AA is the most frequent among obese subjects (86.4%) for (TLR4D299G, A > G) and the homozygous CC genotype is the most frequent (92.4%) for (TLR4T399I, C > T). Haplotype analysis of TLR4 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; p-value = 0.016). The monocyte cell surface of TLR4 was significantly higher by 1.3 folds in obese compared to non-obese subjects. CONCLUSIONS: TLR4 D299G/T399I haplotype polymorphism is associated with an increased risk of insulin resistance with the upregulation of TLR4 protein expression in obese subjects.

Cesarean Scar - Unusual Site of Ectopic Pregnancy: A Case Report.

Ectopic pregnancy is a leading cause of maternal mortality in the first trimester. It may occur in different anatomic locations with fallopian tube being the most frequent. Cesarean-scar ectopic pregnancy is one of the rarest ectopic pregnancies. We report the case of a 44-year-old woman, gravida 5 para 4, who attended the antenatal clinic after her pregnancy was confirmed by positive urine testing. She underwent transvaginal ultrasound examination which identified the gestational sac with fetal pole and cardiac activity located in the anterior part of the lower uterine segment with empty uterine cavity. Magnetic resonance imaging (MRI) scan had confirmed the diagnosis of cesarean scar ectopic pregnancy. After through discussion on the management options, the patient was treated with intra-gestational sac injection of methotrexate. Four days after the procedure, she developed profuse vaginal bleeding and her hemoglobin showed a drop of 4.9 g/dL. She underwent emergency laparotomy with excision of the ectopic pregnancy. The patient tolerated the procedure well without complications. The serum ß-human chorionic gonadotropin level was undetectable on the 35th day after the methotrexate injection. Caesarean scar pregnancy is an unusual form of ectopic pregnancy. However, clinicians should have a high index of suspicion for this condition as it may result in serious complications, unless promptly managed. MRI is recommended particularly when transvaginal ultrasound scan is inconclusive.