Identification of an Interactive Effect of β3- and α2b-Adrenoceptor Gene Polymorphisms on Fat Mass in Caucasian Women

Abstract

/Glu 9 ␣2bAR variant on body composition and energy balance, in a large cohort of Caucasian women (n = 909). A second goal was to examine the interaction effect of Glu 12 /Glu 9 ␣2bAR and Trp64Arg ␤3AR on the same phenotypes. The obesity-related phenotypes studied were as follows: body weight, BMI, fat mass, visceral fat, fat-free mass, resting metabolic rate (RMR), VO 2max , leisure time physical activity, and daily energy intake. Body composition and body fat distribution were measured by dual-energy X-ray absorptiometry and radiographic imagery, VO 2max by a treadmill test to exhaustion, and RMR by indirect calorimetry. An analysis of covariance indicated that in the entire cohort, there was no significant difference between Glu 12 /Glu 9 ␣2bAR carriers and control subjects for any of the obesity-related phenotypes that were examined. However, we observed a significant interaction effect of the Trp64Arg and Glu 12 /Glu 9 variants on fat mass (P = 0.009) and percent fat (P = 0.016). Age, height, body weight, BMI, fat-free mass, visceral fat, energy expenditure, respiratory quotient, physical fitness, and energy intake were not different among groups. Collectively, these findings support an interaction effect of the two adrenoceptor variants on body fatness in Caucasian women, although the physiological mechanism by which they exert this effect remains to be determined. Diabetes 50:91-95, 2001 M ore than 50% of U.S. adults are overweight, with a BMI >25 kg/m 2 (1), suggesting a chronic imbalance between energy expenditure and energy intake. Because of the association of obesity with numerous metabolic comorbidities, it is of considerable public health importance to understand its genetic and environmental determinants. Associations have been demonstrated between several gene variants and obesity, but a simple Mendelian inheritance pattern, as observed in some inbred rodent strains (2), has not been found in humans with typical obesity.Our laboratory has participated in a series of prospective interventional studies that examined the association between the Trp64Arg ␤3AR variant in the ␤ 3 -adrenoceptor gene, with several obesity-related phenotypes. We and others have shown reduced energy expenditure (3-6), insulin resistance (7), a reduced ability to mobilize visceral fat (8), a lower rate of glucose disposal (9), and greater visceral obesity (7) and BMI (6) in individuals harboring the Trp64Arg variant. On the other hand, others have found no meaningful effect of this variant on obesity-related phenotypes (10,11).Because it is recognized that the genetic component of human obesity is complex and polygenic, it is reasonable to hypothesize that the examination of only one genetic variant provides insufficient information regarding genetic susceptibility to obesity. Moreover, we would suggest that discrepancies found in aforementioned studies regarding the effect of the Trp64Arg ␤3AR variant on obesity-related phenotypes may be partially attributed to the presence of other genetic variants that may interact with ...

Interactions among the β2- and β3- adrenergic receptor genes and total body fat and abdominal fat level in the HERITAGE Family Study

“…For instance, an interaction effect of b3-and a2B-adrenergic receptor (ADR) genes on fat mass in Caucasian women has been observed. 8 In addition, gene-gene interaction effects between a2A-, b2-and b3-ADR gene markers on the phenotypic variability of abdominal obesity and plasma lipid levels were observed in the Quebec Family Study cohort. 7 In the present study, we investigated the interactions among polymorphisms in the b2-and b3-ADR genes on total body adiposity and abdominal fat levels in the sedentary state and in response to endurance training in the HERITAGE Family Study cohort.…”

Autonomic Nervous System Pharmacogenomics: A Progress Report

“…The interactive effect of the Glu deletion (heterozygous Glu12/Glu9 allele) in the ␣ 2B -AR and a Trp64Arg polymorphism in the ␤ 3 -AR (to be described below) on energy metabolism and body composition has been examined in healthy women; a significant interaction of the ␣ 2B -and the ␤ 3 -AR variants with greater fat mass and percentage of fat was identified (Dionne et al, 2001). Such results suggest that these two AR variants interact in the regulation of body composition, but studies in larger and more ethnically diverse populations are required.…”

ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics

“…Many studies have shown that the ADR genes are correlated with obesity-related phenotypes. These include the ADRA2B, 18,19 ADRB1, 20,21 ADRB2 18,22-29 and ADRB3 genes. 18,19,28,30,31 Remarkably, most clinically effective antipsychotic drugs are potent ADRA1 antagonists.…”

“…These include the ADRA2B, 18,19 ADRB1, 20,21 ADRB2 18,22-29 and ADRB3 genes. 18,19,28,30,31 Remarkably, most clinically effective antipsychotic drugs are potent ADRA1 antagonists. 32 A possible role of the ADRA1A promoter region in the development of schizophrenia was found in an isolated Spanish population, 33 but not in the Chinese population.…”