Influence of the β2-adrenergic receptor Arg16Gly polymorphism on longitudinal changes in obesity from childhood through young adulthood in a biracial cohort: the Bogalusa Heart Study

Abstract

BACKGROUND:The b2-adrenergic receptor (ADRB2) plays a major role in regulating energy expenditure by stimulating lipid metabolism in human adipose tissue. Polymorphisms in the ADRB2 gene have been associated with obesity and various weightrelated traits in cross-sectional studies of adults, but little is known about the effects of the ADRB2 gene on childhood obesity or the propensity to gain weight over time. OBJECTIVE: To assess the effects of a polymorphism in codon 16 (Arg16?Gly) of the ADRB2 gene, which has been associated with a decrease in b2-receptor density and efficiency, on longitudinal changes in obesity from childhood to young adulthood in a biracial cohort. DESIGN: Seven cross-sectional screenings of children and five cross-sectional screenings of young adults who were previously examined as children produced longitudinal data from childhood to young adulthood. METHODS: Height, weight and subscapular and triceps skinfolds were measured by trained examiners following identical protocols over the course of the study. Gender-and age-stratified analyses using random coefficients models were used to examine longitudinal genetic effects on obesity in 1151 African-American and Caucasian males and females who attended an average of six examinations over a 24 y period from childhood to young adulthood. RESULTS: Age-stratified analyses showed no clear genetic relationships with changes in obesity measures over time in females, but an age-dependent association was observed in males, where the relationship between the Arg16Gly polymorphism and obesity became stronger with age. In males who were 4 -9 y of age at the beginning of the study in 1973, body mass index (BMI) was 4% higher in Gly=Gly and Arg=Gly males compared to those with Arg=Arg by 26 y of age. Subscapular skinfold measurements in Gly=Gly males became significantly different from Arg=Arg males (20% higher) by age 20. In the oldest male cohort (10 -14 y of age in 1973), BMI increased at a significantly greater rate (0.4%=y) in males carrying the Gly16 form of the receptor relative to Arg=Arg males. BMI was significantly different between homozygous genotypes by approximately 26 y of age, and reached 8% higher in Gly=Gly males by age 32. Subscapular skinfolds also increased at a significantly greater rate (2%=y) in Gly=Gly males compared to Arg=Arg males, becoming significantly different (27%) by approximately 22 y of age and reaching a maximum difference of 50% by age 32. CONCLUSIONS: Our data suggest that the b2-adrenergic receptor is associated with the propensity to gain weight from childhood to young adulthood in males. An increased understanding of genetic influences on the development of obesity may improve the effectiveness of interventions designed to reduce excess body weight and help define the role of genetic factors in diabetes and cardiovascular disease.

Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes

“…Polymorphisms located within β2-adrenergic receptor have been associ- ated with obesity in various ethnic groups [31]. One mutation known to decrease receptor density and efficiency is Arg16Gly, which is associated with longitudinal increases in weight gain in a large cohort of male children [32]. In other studies, the same mutation has been associated with a greater relative risk for developing Type 2 diabetes [33].…”

Candidate genes and growth curves for adiposity in African- and European-American youth

“…Two of these studies have examined weight gain in which weight was measured only twice (for example, van Rossum et al 33,34 ). Three studies have examined candidate gene associations with weight gain in longitudinal studies with adiposity measured over several years, 9,35,36 all of which focus on b-adrenergic receptors. The Bogalusa Heart study 9 has found suggestive evidence for increased weight gain from childhood to young adulthood in male carriers of the Gly allele of the ADRB2 Arg16Gly polymorphism, and this increase in weight gain is potentially dependent on b1-adrenergic receptor genotype.…”

“…Only one study investigated the relationship between a candidate gene and longitudinal changes in adiposity from childhood to young adulthood. 9 However, this study did not include measures of central obesity, focused on just a single polymorphism and did not examine potential interactions with environmental determinants of obesity such as socioeconomic status (SES).…”

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

“…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.…”