Synergistic effect of polymorphisms in uncoupling protein 1 and β3-adrenergic receptor genes on long-term body weight change in Finnish type 2 diabetic and non-diabetic control subjects

Abstract

OBJECTIVE: To investigate the independent and combined effects of the Trp64Arg polymorphism of the b b 3 -adrenergic receptor (b b 3 AR) gene and the (À3826) A?G polymorphism of the uncoupling protein 1 (UCP1) gene on body weight change in type 2 diabetic and non-diabetic control subjects during a 10 y follow-up study. DESIGN: Controlled 10 y follow-up study with baseline, 5 and 10 y examinations. SUBJECTS: 70 newly diagnosed, middle-aged type 2 diabetic patients and 123 non-diabetic control subjects from eastern Finland. MEASUREMENTS: Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma C-peptide and HbA 1c . Genotypes by polymerase chain reaction followed by enzymatic digestion. RESULTS: No signi®cant differences were found in the frequencies of the two polymorphisms between diabetic and control subjects. The polymorphisms were not cross-sectionally or longitudinally associated with body weight or BMI in diabetic or control subjects. When the diabetic and control subjects were analysed together, the change in the mean body weight was signi®cantly greater among the subjects with both polymorphisms (n 11) than among those with no polymorphisms (n 103; change in weight 6.5 AE 2.5% vs À0.2 AE 0.8%, P 0.036, and change in Body Mass Index 8.5 AE 2.6% vs 2.0 AE 0.8%, P 0.060, mean AE s.e.m.). CONCLUSIONS: The simultaneous existence of the two polymorphisms was associated with a tendency to gain weight suggesting a synergistic effect of these polymorphisms on body weight gain.

Gene–gene interaction between PPARγ2 and ADRβ3 increases obesity risk in children and adolescents

“…In the literature, several studies reported the existence of a positive interaction for weight gain between ADRb3 and UCP1 gene variants. [16][17][18] But there is only one previous report concerning ADRb3 and PPARg2 gene variants interactions. In a cross-sectional study, Hsueh et al 11 found a gene  gene interaction between polymorphisms Pro12Ala of the PPARg2 gene and Trp64Arg of the ADRb3 gene.…”

β3-Adrenergic receptor Trp64Arg polymorphism and increased body mass index in sleep apnoea

“…Recent evidence suggests that the Arg64 ADRB3 variant has additive and interactive effects with a number of other candidate gene variants, such as the uncoupling protein 1 and 2 genes and lipoprotein lipase gene [25][26][27]. Furthermore, it has been suggested that the sleep disruption that characterises OSAS may influence the expression of these genes and thus the relative importance of a variant at these loci in determining the obesity risk [5].…”

Multifactor-dimensionality reduction shows a two-locus interaction associated with Type 2 diabetes mellitus

“…The ADRB3 gene has been the gene most frequently examined and reported in connection with gene to gene interaction, e.g. with UCP1 gene in Danish [16] and in Finnish populations [17], with the human type 2 deiodinase gene in white populations [18], with the FABP2 gene in Japanese [19] and with the PPARγ2 genes in Mexican American populations [20]. In a different way, using multi-point allele-sharing analysis with lod score, other investigators showed that the loci on chromosome 2 (NIDDM1) and 15 (near CYP19) interact to increase susceptibility to Type 2 diabetes in Mexican Americans [21].…”