β 2-adrenoceptor gene polymorphism, body weight, and physical activity

Abstract

Lipolysis activation and inhibition modulate body weight, body fat, and obesity. These metabolic pathways are influenced by environmental factors, such as physical activity, and by genetic determinants associated with sequence polymorphisms of proteins involved in lipolysis. Among these proteins, adrenergic receptors, activated by catecholamines, play a major part: b-adrenoreceptors stimulate while a2adrenoreceptors inhibit lipolysis in fat. Polymorphisms in the coding sequence of the b2-adrenoreceptor ( B A R 2 ) gene have been associated with obesity, increased body mass index (BMI) and body fat. In a large representative sample of the northern French p o p u l a t i o n , we explored the influences of the B A R 2 Gln27Glu polymorphism and of physical activity on anthropometric variables and obesity (BMI >30 kg/m) . Individuals were randomly sampled from the electoral rolls between 1995 and 1997 (n=1195), equally distributed in tenyear age groups (35 to 64 y) and by gender. For each individual, weight, height, waist and hip circumferences, and physical activity were collected. Physical activity was defined as at least 15 min walk a day, and/or lifting or carrying heavy objects at work daily, and/or doing sport or physical exercise more than 2 h a week. Genotypes for the Gln27Glu polymorphism were obtained for 1152 men and women. Individuals who were taking no medical treatments likely to interfere with body weight were selected (n=836, age=49·5 [SD 8·1] years, BMI=25·7 [4·4] kg/m). Data were analysed by multivariate covariance and logistic regression. Statistical analyses were stratified on gender and were adjusted on age and consumption of cigarettes and of alcohol. Genotype and allele frequencies were in Hardy-Weinberg equilibrium (Gln27Gln 33·1%, Gln27Glu 51·0%, and Glu27Glu 15·9%, Gln allele frequency 0·59) and were similar in men and women. A statistically significant interaction was detected between the Gln27Glu polymorphism and physical activity for body weight (p=0·009), BMI (p=0·007), waist (p=0·03) and hip (p=0·01) circumference in men, but not in women. We analysed the effect of the Gln27Glu polymorphism in men, stratified on physical activity (figure). In men who did not take physical activity (n=255), Gln27Gln men (n=91), compared with Glu27 carriers (n=164), had higher body weight (adjusted mean 83·2 [SEM 1·3] v s 7 6 · 3 [1·0] kg, p=0·0001), BMI (27·2 [0·4] v s 25·2 [0·3] kg/m, p=0·0001), waist circumference (98·7 [1·0] v s 93·2 [0·7] cm, p=0·0001), hip circumference (103·0 [0·7] v s 100·0 [0·5] cm, p=0·0007) and waist to hip ratio (0·96 [0·01] v s 0·93 [0·01], p=0·002) (figure). Conversely, no effect of the Gln27Glu polymorphism was found in men who took regular physical activity (n=165). In men taking no physical activity, the risk of obesity associated with the Gln27Gln genotype was 3·45 (95% CI 1·56–7·80, p=0·002), while this risk was not significantly increased in men who took regular physical activity (OR 1·61, 95% CI 0·67–3·87, p=0·30). We have shown that physical activity may counterbalance the effect of a genetic predisposition to increase body weight, body fat, and obesity. Obese individuals with the B A R 2 Gln27Gln genotype may benefit from physical activity to reduce their weight. Genotyping may be a useful tool to target prevention such as physical activity, to individuals that have highest benefit from it. 1 Mauriege P, Prud’homme D, Marcotte M, Yoshioka M, Tremblay A, Despres JP. Regional differences in adipose tissue metabolism between Effects of the Gln27Glu polymorphism in men according to physical activity. Statistical tests were adjusted on age, and alcohol and tobacco consumptions. Data are mean and SEM. Black bars represent Gln27Gln individuals and white bars Gln27Glu+Glu27Glu individuals.