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

OBJECTIVES: The β-adrenergic receptor (βAR) 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 β₁AR (ADRB1), β₂AR (ADRB2), β₃AR (ADRB3), Gs protein alpha (GNAS1), to which all three β-receptors couple and the G protein β3 subunit (GNB3), to which β₃ARs 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 βAR 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 βARs 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.