POLYMORPHISM OF THE BETA(3)-ADRENERGIC RECEPTOR GENE IN MORBID-OBESITY

OBJECTIVE: The Trp64 --> Arg allele of the beta(3)-adrenergic receptor gene was recently proposed to be associated with an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), features of insulin r esistance and a tendency to gain weight. We investigated whether the A rg64 allele predisposes to severe obesity. DESIGN AND SUBJECTS: A gene tic association study of 254 subjects with morbid obesity [body-mass i ndex (BMI) greater than or equal to 40; mean 42.8 +/- 7.0] and 151 lea n healthy control subjects [BMI less than or equal to 25: mean BMI 22. 3 +/- 1.9]. MEASUREMENTS: beta(3)-adrenergic receptor genotyping was c arried out with a solid-phase minisequencing technique. Serum lipids, glucose and insulin levels in the obese subjects were also determined. RESULTS: The frequency of the Arg64 did not significantly differ in t he morbidly obese patients (9.1%) and lean controls (8.9%), nor was th ere any statistically significant association between the mean BMI val ues and the beta(3)- adrenergic receptor genotype. However, obese subj ects carrying the Arg64 allele developed obesity more often before the age of 15 y than those without it (P < 0.05, adjusted for multiple co mparisons). The frequency of the Arg64 allele was similar in nondiabet ic and diabetic patients; the mean age at the onset of NIDDM did not d iffer according to the beta(3)-adrenergic receptor genotype. There was no significant association between the receptor genotype and the leve l of the serum cholesterol, HDL-cholesterol, triglyceride, glucose or insulin, nor was this polymorphism associated with the behavioural or psychopathological characteristics of the morbidly obese subjects. Res ponse to a 16w treatment program including a very-low calorie diet (VL CD) regimen, dietary and exercise counseling, as well as behavioural m odifications, did not differ according to the genotype. CONCLUSION: Ou r data do not support a significant role for the codon 64 polymorphism of the beta(3)-adrenergic receptor as a genetic marker of morbid obes ity. Although there was an association between the Arg64 allele and an earlier onset of obesity in individuals subsequently developing morbi d obesity, this allele was not associated with the actual BMI gained o r response to weight-loss therapy on a hypocaloric diet.