Association of adipose tissue deposition and beta-2 adrenergic receptor variants: the IRAS family study

Abstract

OBJECTIVE: Adipose tissue distribution (visceral vs subcutaneous) has been shown to be an important predictor of insulin resistance, diabetes and cardiovascular disease, independent of body mass index. The beta-2 adrenergic receptor is a major lipolytic receptor in human fat cells and the gene that codes for this protein is an important candidate gene for measures of adiposity and fat deposition. We examined whether two common polymorphisms in codons 16 (Arg16Gly) and 27 (Gln27Glu) are associated with measures of fat distribution in participants of the IRAS Family Study. METHODS: We recruited African-American (AA) and Hispanic-American (HA) families from Los Angeles, CA, USA (18 pedigrees, 272 AA individuals), San Antonio, TX, USA (33 pedigrees, 448 HA individuals) and San Luis Valley, CO, USA (12 pedigrees, 272 HA individuals). We estimated adipose tissue distribution via computed tomography. To test for an association between adiposity measures and these polymorphisms, we used generalized estimating equations, adjusting for age, gender, clinical site (ethnicity), body mass index, and familial correlation. RESULTS: Of the 992 individuals genotyped for these polymorphisms, 57% were female and 15% had been diagnosed with type 2 diabetes mellitus. The mean age was 42.7714.6 y. The Glu27 allele of the Gln27Glu polymorphism was positively associated with (P-value for recessive model): body mass index (0.025), visceral adipose tissue (o0.0001) and visceral-tosubcutaneous adipose ratio (0.009), but not with subcutaneous adipose tissue (0.952). The Arg16Gly polymorphism was not associated with any of the adiposity measures. CONCLUSIONS: These findings suggest that genetic variation in the beta-2 adrenergic receptor gene influences fat deposition and body size in AAs and HAs. In particular, these results support a role for the gene in the distribution of visceral adipose tissue but not subcutaneous adipose tissue.

Influence of ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms on body weight and body composition changes after a controlled weight-loss intervention

“…Several studies, in agreement with our results, did not find association between the Gln27Glu polymorphism of the ADRB2 gene and obesity or related parameters (Bea et al 2010;Echwald et al 1998;Kortner et al 1999). Most positive findings with the Gln27Glu polymorphism suggest that the favorable allele is the Gln27 allele, and the Glu27 allele contributes to obesity risk (Clement et al 1995;Gonzalez Sanchez et al 2003;Lange et al 2005;Large et al 1997). Contrary, other researchers showed that the Gln27 allele enhances the risk of obesity (Meirhaeghe et al 2000;Pereira et al 2003).…”

“…While some researchers found that the Glu27 is the risk allele for obesity (Clement et al 1995;Gonzalez Sanchez et al 2003;Lange et al 2005;Large et al 1997), on the contrary others reported that the Glu27 is the favorable allele, protective against obesity (Meirhaeghe et al 2000;Pereira et al 2003).…”

The search for putative unifying genetic factors for components of the metabolic syndrome

“…Second, we investigated ten polymorphisms in nine genes (ADRB1, ADRB2, ADRB3, CAPN10, IRS1, UCP2, PPARGC1A, PTPN1 and ENPP1), each of which has been associated with at least two components contributing to the metabolic syndrome [19][20][21][22][23][24][25][26][27][28][29][30][31][32].…”

Dieta hiperlipídica e capacidade secretória de insulina em ratos

“…nos ratos do grupo H, uma vez que o acúmulo de gordura na região abdominal tem sido relatado como fator determinante no desenvolvimento da resistência à insulina, e por ser este tecido metabolicamente mais ativo do que o tecido adiposo periférico 21,22 . O aumento do peso relativo do TAM nos ratos alimentados com a dieta hiperlipídica (Tabela 1), comparado aos controles, é concordante com outros estudos da literatura 19,23,24 .…”