Association between β-adrenergic receptor polymorphisms and their G-protein-coupled receptors with body mass index and obesity in women: a report from the NHLBI-sponsored WISE study

Abstract

OBJECTIVES:The b-adrenergic receptor (bAR) genes are candidate genes for obesity because of their roles in energy homeostasis and promotion of lipolysis in human adipose tissue. Objective is to determine the association between obesity and polymorphisms in genes of the b 1 AR (ADRB1), b 2 AR (ADRB2), b 3 AR (ADRB3), Gs protein alpha (GNAS1), to which all three b-receptors couple and the G protein b3 subunit (GNB3), to which b 3 ARs couple. DESIGN: A case-control genetic association study. SUBJECTS: A total of 643 black or white women enrolled in Women's Ischemia Syndrome Evaluation (WISE) study. MEASUREMENTS: Genotypes were determined by PCR with single primer extension. Associations between genotype and body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, and obesity were made. RESULTS: Polymorphisms in the three bAR genes, GNAS1, and GNB3 were not associated with BMI, WHR, waist circumference, or obesity. Linear and logistic regression analyses found no contribution of either genotype or haplotype with anthropometric measurements or obesity. CONCLUSIONS: Our study suggests that among American women with suspected coronary heart disease, polymorphisms in the bARs and their G-protein-coupled receptors do not contribute to increased BMI, WHR, waist circumference, or obesity. Given that 50% of all women die from coronary heart disease, and a higher percentage have heart disease during their lifetime, our results are likely generalizable to many American women.

The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases

“…The associations for our African American set of cases and two other AfricanAmerican populations 27,28 were found with the wild-type allele, whereas the ADRB3-weight association in white and Japanese populations has been described with the variant allele. Although some experimental studies suggest that carriers of the Arg variant may have reduced fat metabolism, the functional role of the missense is not yet established, nor do we know how lifestyle or other lipid metabolism pathway genes influence the ADRB3-weight association.…”

“…Consistent with our data, Lowe Jr et al 27 reported a protective association between the variant allele and BMI among African-American women (P ¼ 0.04). Similarly, Terra et al 28 reported that African Americans who were homozygous for the wild-type allele had higher mean BMI than variant carriers, although the association did not reach statistical significance. In contrast, McFarlane-Anderson et al 29 found that Jamaican women who were carriers of the variant allele had a significantly increased BMI than women who were homozygous for the wild-type allele.…”

Gene–environment interaction and the GNB3 gene in the Atherosclerosis Risk in Communities Study

“…Other studies have reported positive associations between the GNB3 825C4T polymorphism and obesity in populations of Germans, 2 Chinese, black South Africans 21 and Canadian Nunavut Inuit, 22 whereas several studies have reported no association between this gene variant and obesity, [23][24][25][26][27] including ARIC whites. Few studies have considered the effect of gene-physical activity interaction when testing the GNB3 825C4T polymorphism for association to disease.…”

β-Adrenergic receptor gene polymorphisms and hemodynamic response to dobutamine during dobutamine stress echocardiography

“…Genotypes were determined by one of three methods: Orchid BioSciences Inc.'s (Princeton, NJ, USA), proprietary single primer extension technology (SNP-IT), pyrosequencing or polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). Single primer extension 22 16 and b 2 -AR codon 27, respectively. PCR-RFLP for b 1 -AR codons 49 and 389 was conducted according to previously described methods using the Sau96I and BstNI restriction enzymes, respectively.…”