Abstract
BackgroundIn some populations, obesity and body weight related disorders show a correlation with polymorphisms in three subtypes of beta-adrenoceptor (β1, β2, and β3) [ADRB1, ADRB2 and ADRB3] genes. We scanned for the polymorphism of Arg389Gly (rs1801253) in ADRB1 and Trp64Arg (rs4994) in ADRB3 genes in Saudi population to determine association, if any, of these polymorphisms with obesity and related disorders.MethodsWe studied 329 non-related adults (33.1% men and 66.9% women), aged 18–36 years. Anthropometric measurements were recorded, and Body mass index (BMI) and waist/hip ratio were calculated; leptin, insulin, lipidogram, and glucose concentrations were determined. ADRB1 and ADRB3 polymorphisms (Arg389Gly and Trp64Arg, respectively) were screened by DNA sequencing. The subjects were divided into three groups according to BMI: normal weight (BMI < 25 kg/m2), overweight (BMI ≥25.1–29.9 kg/m2) subjects, and obese (≥30 kg/m2).ResultsIn the age-matched groups of the normal weight, overweight and obese male and female subjects, all anthropometric parameters were found to be significantly higher, and in the obese group, all biochemical parameters were significantly elevated compared to the normal weight controls. The allelic frequency of Gly389 ADRB1 did not differ amongst the three groups, whereas the frequency of Arg64 of ADRB3 gene was significantly higher in the overweight and obese subjects, compared with the normal weight subjects. In addition, subjects carrying Arg64 allele regardless of their BMI had a greater waist and hip circumference, W/H ratio, plasma cholesterol, triglyceride, LDL, leptin, insulin, and glucose level compared to those with the wild-type Trp allele.ConclusionThe results of this study have shown a significant association between the Trp64Arg polymorphism in ADRB3 gene and the development of overweight and obesity in Saudi populations. It also has an influence on the levels of lipid, insulin, leptin, and glucose, whereas, Arg389Gly polymorphism in ADRB1 is not associated with overweight, obesity or dyslipidaemias in Saudis.
Highlights
In some populations, obesity and body weight related disorders show a correlation with polymorphisms in three subtypes of beta-adrenoceptor (β1, β2, and β3) [ADRB1, β2 beta-adrenoceptor (ADRB2) and β3 betaadrenoceptor (ADRB3)] genes
20 ml of blood was drawn by venipuncture from an antecubital vein without compression, following an overnight fast, from each subject under study. 10 ml blood was placed in ethylenediaminetetraacetic acid (EDTA) coated tubes, 2 ml in tubes containing fluoride and the rest in plain tubes
Since in our previous report, we had observed an association between Gln27Glu polymorphism of ADRB2 gene, obesity, and other related disorders in Saudi population [9] our interest was to explore if any association existed between ADRB1 and ADRB3 and these abnormalities
Summary
Obesity and body weight related disorders show a correlation with polymorphisms in three subtypes of beta-adrenoceptor (β1, β2, and β3) [ADRB1, ADRB2 and ADRB3] genes. We scanned for the polymorphism of Arg389Gly (rs1801253) in ADRB1 and Trp64Arg (rs4994) in ADRB3 genes in Saudi population to determine association, if any, of these polymorphisms with obesity and related disorders. Extensive studies have linked different genetic loci to obesity, and strong linkage has between reported between beta (β) adrenoceptor polymorphisms (ADRB) and obesity or weight gain [6,7,8,9,10]. It has been shown that ARDBs are polymorphic with single nucleotide polymorphism (SNPs) exerting functional consequences affecting receptor activity and regulation, and may contribute to the pathophysiology of obesity and related disorders [7,8,9]. Several studies have shown an association between ADRB polymorphism and BMI, T2DM, hypertension [HT] and dyslipidaemias, while other studies have failed to show such an association [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53]
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