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Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations.

ABSTRACT: Genes involved in the regulation of catecholamine function may be important in obesity because of the role catecholamines play in energy expenditure and lipolysis. To determine if common single nucleotide polymorphisms (SNPs) in beta(1)-adrenergic receptor (ADRB1), beta(2)-adrenergic receptor (ADRB2), beta(3)-adrenergic receptor (ADRB3), and alpha(2)-adrenergic receptor (ADRA2A) genes associate with obesity and metabolic alterations, we recruited 74 healthy African American and 161 white men and women (age, 18-49 years) to participate in this case-control genetic association study. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. Associations between genotype and body mass index (BMI), percentage of body fat (by measuring skinfold thickness in 7 different sites), fasting (12-hour) plasma glucose, insulin, potassium concentrations, glycated hemoglobin, and insulin resistance (homeostasis model assessment [HOMA(IR)] score) were performed. Among whites, the ADRB1 Arg389-->Gly variant associated with insulin concentrations and HOMA(IR): mean +/- SD values for insulin and HOMA(IR) in Arg389 homozygotes and carriers of the Gly were 10 +/- 7.0 and 12 +/- 9.4 micro IU/mL (P = .02) and 2.1 +/- 1.7 and 2.6 +/- 2.2 (P = .057), respectively. Systolic blood pressure was higher in whites for carriers of the ADBR1 Ser49 compared to Gly49 homozygotes (124 +/- 12.6 vs 119 +/- 11.3 mm Hg, respectively; P = .02). Subsequent analysis revealed that these associations were attributable to a higher BMI among obese participants. The ADRA2A G1780A SNP associated with BMI and percentage of body fat in African Americans (P = .05). Interactions were detected between ADRA2A C-1291G and ADRB2 Gln27-->Glu variants for obesity in African Americans and between ADRA2A C-1291G SNP and ADBR1 haplotype for obesity in whites. We conclude that common SNPs in adrenergic receptor genes may be important susceptibility loci for obesity and related alterations. Because of the limited size of our populations, our results should be interpreted with caution and should be replicated in larger populations.

SUBMITTER: Lima JJ

PROVIDER: S-EPMC2040233 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

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Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations.

Lima John J JJ Feng Hua H Duckworth Laurie L Wang Jianwei J Sylvester James E JE Kissoon Niranjan N Garg Hardesh H

Metabolism: clinical and experimental 20070601 6

Genes involved in the regulation of catecholamine function may be important in obesity because of the role catecholamines play in energy expenditure and lipolysis. To determine if common single nucleotide polymorphisms (SNPs) in beta(1)-adrenergic receptor (ADRB1), beta(2)-adrenergic receptor (ADRB2), beta(3)-adrenergic receptor (ADRB3), and alpha(2)-adrenergic receptor (ADRA2A) genes associate with obesity and metabolic alterations, we recruited 74 healthy African American and 161 white men and ...[more]

PMID: 17512307

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Project description:BACKGROUND: Prevalence of obesity is increasing all over the world. ADRB3 Trp64Arg gene polymorphism was proposed to be associated with obesity, although inconsistent findings and differences of the Arg64 allele frequency among various ethnics were reported. Westernization was reported to increase the prevalence of obesity in developing world. In this study we determined the prevalence of obesity and metabolic syndrome among urban and rural Balinese, and studied the association of ADRB3 Trp64Arg polymorphism with obesity and MetS. FINDINGS: A total of 528 Balinese (urban 282, rural 246) were recruited. Body mass index (BMI) and waist circumference (WC) were determined; high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic and diastolic blood pressure (SBP and DBP), and fasting plasma glucose (FPG) were measured using standard procedures. BMI and WC classifications were based on WHO classifications for Asian. Metabolic syndrome (MetS) was defined as described in the Joint Interim Statement. Chi-square test was employed to test the association between the ADRB3 Trp64Arg genotype and disease traits.Urban have higher BMI (p = 2.8 × 10-13), WC ( p < 2.2 × 10-16), TG (p = 0.0028), DBP (p = 1.8 × 10-5), and lower HDL-C (p = 0.0376) when compared to rural. Abdominal obesity and MetS prevalence were significantly higher in urban as compared to rural (both p < 0.001). The Arg64 allele frequency was similar between urban (0.06) and rural (0.05). The Arg64 rural female carriers have higher BMI and WC as compared to their Trp64 counterparts (p = 0.041 for BMI and p = 0.012 for WC), and consequently higher abdominal obesity prevalence (p = 0.007). Comparison between male and female, as well as urban and rural, showed different prevalence of MetS co-morbidities. Abdominal obesity and hypertriglyceridaemia were consistently appeared in all groups, suggesting to play a role as determinant of MetS in both urban and rural. CONCLUSIONS: Prevalence of obesity and MetS in urban were two times higher when compared to rural. Abdominal obesity and hypertriglyceridaemia appears to be the key determinant of MetS in both urban and rural Balinese. Our results indicated an association of the ADRB3 Trp64Arg gene polymorphism with obesity in the rural female.

Project description:BackgroundPrevious studies have suggested that fat mass-and obesity-associated (FTO) gene is associated with body mass index (BMI) and the risk of obesity. This study aims to assess the association of five FTO polymorphisms (rs9939609, rs8050136, rs1558902, rs3751812 and rs6499640) with obesity and relative parameters in Han Chinese adolescents.MethodsWe examined a total of 401 adolescents, 223 normal weights (58.7% boys, 41.3% girls), 178 overweight (60.1% boys, 39.9% girls), aging from 14 to 18-years-old, recruited randomly from public schools in the central region of Wuxi, a southern city of China. DNA samples were genotyped for the five polymorphisms by Sequenom Plex MassARRAY. Association of the FTO polymorphisms with BMI, serum fasting plasm glucose (FPG), fasting insulin (FIns), triglyceride (TG) and cholesterol (TC) were investigated.Results1) Serum FPG, FIns, TG and TC were statistically significant higher than that in normal control group. 2) We found that BMI was higher in the rs9939609 TA+AA, rs8050136 AC+AA, rs1558902 TA+AA and rs3751812 GT+TT genotypes than in wild TT genotypes (rs9939609: P = 0.038; rs1558902: P = 0.038;), CC genotypes(rs8050136: P = 0.024) and GG genotypes (rs3751812: P = 0.024), which were not significant on adjusting for multiple testing. 3) In case-control studies, five polymorphisms were not significantly associated with overweight (p>0.05), haplotype analyses showed non-haplotype is significantly associated with a higher risk of being overweight (p>0.05). 4) There existed no significant statistical difference about FPG, FIns, TG and TC in genotype model for any SNP.ConclusionsOur study has conducted a genetic association study of the FTO polymorphisms with BMI, serum fasting plasm glucose (FPG), fasting insulin (FIns), triglyceride (TG) and cholesterol (TC). Our study found BMI of subjects with A allele of FTO rs9939609 is higher than that with T allele. Further studies on other polymorphisms from FTO and increasing the sample size are needed.

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Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations.

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Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations.

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