Impact of polymorphisms of the human β2-adrenoceptor gene on obesity in a French population

Abstract

OBJECTIVE: To investigate the impact of two common polymorphisms in the human b b 2 -adrenoceptor gene (Gly16Arg and Gln27Glu substitutions) on obesity and anthropometric measurements as well as blood variables in a large sample of a French population. DESIGN AND SUBJECTS: Within the framework of the WHO-MONICA project, a population study composed of 1195 subjects aged 35 ± 64 y was randomly sampled from the electoral rolls of the Urban Community of Lille, in northern France. Subjects without any medical treatment (for hypercholesterolaemia, hypertension or diabetes mellitus) susceptible to interfere with body weight and biological variables were selected (n 836, 419 mena417 women, age 49.5 AE 8.1 y, body mass index (BMI) 25.7 AE 4.4 kgam 2 ). Subjects with a body mass index ! 30 kgam 2 were considered as obese (n 119, age 49.5 AE 8.2 y, BMI 33.9 AE 3.3 kgam 2 range 30 ± 44). MEASUREMENTS: Genotyping was carried out with allele-speci®c oligonucleotides hybridization. Association between genotypes and various obesity markers (body weight, body mass index, waist and waist-to-hip ratio), lipid, glucose and insulin variables were studied. RESULTS: The Gly16Arg and Gln27Glu polymorphisms were in complete linkage disequilibrium. Gln27Gln subjects had an increased risk of obesity (odds ratio (OR) 1.77, 95% CI 1.19 ± 2.62, P 0.005). This effect was mainly detected in men (OR 2.40, 95% CI 1.34 ± 4.27, P 0.003). Men bearing the Gln27Gln genotype had higher body weight, BMI, waist and hip circumferences and waist-to-hip ratio than others. Moreover, if Gln27Gln men carried in addition the Arg16 allele, the increase in body weight, BMI and waist-to-hip ratio was more important. CONCLUSION: Our results suggest that genetic variability of the b b 2 -adrenoceptor gene is implicated in body weight regulation and in the onset of obesity in French men.

Studies of the associations between functional β2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects

“…The present case-control study, quantitative trait analysis and meta-analysis did not provide evidence of an impact of the variant on obesity, which is consistent with previously performed case-control studies [2,[4][5][6][7][8][9]. Previous studies have suggested sex differences [16].…”

“…The Arg allele frequency of the ADRB2 Arg16Gly variant (38%) was similar to previously identified allele frequencies [2,4,5]. The present case-control study, quantitative trait analysis and meta-analysis did not provide evidence of an impact of the variant on obesity, which is consistent with previously performed case-control studies [2,[4][5][6][7][8][9].…”

“…The same ambiguity is observed when the two variants are examined in relation to hypertension [9,10,[12][13][14][15] and type 2 diabetes [2,5,9,14,[16][17][18].…”

“…Several of these failed to identify any association [3][4][5][6][7][8][9]. Other studies have found significant associations [8,10,11], but without a consensus regarding which allele is associated with obesity or related traits.…”

Genetic contributors to obesity

“…Lipolysis of triglyceride stores is regulated by catecholamines and sympathomimetic stimuli via beta-adrenergic receptors, resulting in activation of the cyclic AMP/protein kinase A (cAMP/PKA) cascade, phosphorylation and translocation of hormone-sensitive lipase (HSL) from the cytoplasm to the lipid droplet. Various polymorphisms in the beta2-and beta3-adrenergic receptors have been reported in relationship with obesity (36)(37)(38)(39). The HSL knockout mouse exhibits male sterility and adipocyte hypertrophy but not obesity, as well as normal basal lipolysis but blunted response to catecholamines (40).…”