Abstract
The association between LEP G-2548A gene polymorphism with increased plasma leptin and glucose levels and blood pressure in a sample of obese Saudi patients has been evaluated. This is a cross-sectional study involved 206 Saudi adult subjects (94 males and 112 females), randomly selected from the primary health care centers, Riyadh, Saudi Arabia. The study sample was categorized into three groups: 50 normotensive ND controls (age: 47.9±5.4 yr.; BMI 22.9±2.1 Kg/m2), 80 obese normotensive ND (age: 47.7±6.0 yr.; BMI 34.1±4.2 Kg/m2) and 76 obese hypertensive with T2D patients (age: 49.4±5.9 yr.; BMI: 35.1±4.7 Kg/m2). Analyses of LEP G-2548A gene polymorphism were determined using polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP) with 2U of HhaI restriction enzyme. Plasma leptin and insulin levels were measured using the Luminex instrument. Fasting plasma glucose, total cholesterol, HDL-cholesterol, and triglycerides were measured using a chemical autoanalyzer Konelab machine. Also, blood pressure and anthropometric data were measured. The association analysis with metabolic parameters showed that homozygous AA of the LEP gene had significantly higher plasma glucose levels and HOMA-IR compared with homozygous GG (6.8±0.55 vs. 5.8±0.30; p< 0.04; 4.1±0.84 vs. 2.6±0.67; p=0.03) respectively. Besides, heterozygous GA had significantly higher plasma leptin levels compared with homozygous GG (40.0±2.6 vs. 29.6±2.6; P= 0.04). GA, AA, GA+AA genotypes of the LEP G-2548A gene polymorphism are more prevalent among individuals with hyperglycemia (OR= 3.7, 95% CI= 1.6 to 8.4, P= 0.001; OR= 3.2, 95% CI= 1.2 to 8.6, P= 0.03; OR= 3.5, 95%CI= 1.6 to 7.7, P= 0.001) respectively. A allele of the LEP gene is more prevalent among subjects with hyperglycemia (OR= 1.9, 95%CI= 1.2 to 3.0, P=0.006). G-2548A variant of the LEP gene may not be considered as a genetic risk factor for hypertension in Saudi obese patients. However, the genotypes (GA and AA) and -2548AA allele of this gene may represent important risk factors predisposing healthy subjects to develop T2DM irrespective of the status of blood pressure.