Synergistic effect of polymorphisms of uncoupling protein 1 and β3-adrenergic receptor genes on autonomic nervous system activity

Abstract

OBJECTIVE:To investigate the association of the promoter region 73826 A to G polymorphism of the uncoupling protein 1 (UCP1) gene with autonomic nervous system (ANS) activity and the interaction of the polymorphism with the Trp64Arg polymorphism of the b3 adrenergic receptor (b3AR). SUBJECTS: Three-hundred and forty-nine young (mean age 20.4 AE 2.1 y old), healthy Japanese males. MEASUREMENTS: DNA was extracted from whole blood and genotyped by polymerase chain reaction restriction fragment length polymorphism. Plasma glucose, plasma insulin and body mass index (BMI) were measured. Frequency of family history of diabetes or obesity was determined by interview. Subjects randomly chosen from each genotype were examined for ANS activity during supine rest and standing by electrocardiogram power spectral analysis of heart rate variability. RESULTS: UCP1 or b3AR polymorphism was not associated with BMI, plasma glucose, plasma insulin and frequency of family history of diabetes or obesity. The inhibitory effect of UCP1 polymorphism on ANS activity was observed only with occurrence of the variant of b3AR. The very low frequency component associated with thermoregulation in the sympathetic nervous system of homozygotes of UCP1 (GG) at supine rest was signi®cantly lower than normal (AA, 203.2 AE 50.3 vs 462.2 AE 83.6 ms 2 ; mean AE s.e., P 0.021). A higher response to postural change to standing was also observed in both sympathetic and parasympathetic nervous activities of AA than of GG. CONCLUSION: While UCP1 polymorphism alone does not affect ANS activity, it has a synergistic effect with b3AR polymorphism in decreasing sympathetic nervous system activity.

Impact of UCP1 and β3AR gene polymorphisms on age-related changes in brown adipose tissue and adiposity in humans

“…In fact, the data obtained from old volunteers/patients revealed significant association of UCP1 À 3826 A/G with BMI, 31,32 but those from young subjects showed no association. 33,34 Being consistent these previous reports, our present results demonstrated an impact of the UCP1 gene polymorphism on adiposity-related parameters in older, but not younger, subjects.…”

“…Some studies repoted the association of G allele with obesity, whereas others did not confirm this. [31][32][33][34] Such discrepancy may be owing to analysis without having to take into consideration of possible effects of age-related decline of BAT on obesity development. In fact, the data obtained from old volunteers/patients revealed significant association of UCP1 À 3826 A/G with BMI, 31,32 but those from young subjects showed no association.…”

Autonomic Nervous System Pharmacogenomics: A Progress Report

“…More recently, potentially important interactions between the Trp64Arg ␤ 3 -AR polymorphism and other candidate genes for metabolic disorders have been identified, including synergism with the Ϫ3826 A3 G promoter polymorphism of the uncoupling protein 1 gene, which is associated with decreased sympathetic nervous system activity and a tendency to gain weight (Sivenius et al, 2000;Shihara et al, 2001). In women, a significant interaction between the Trp64Arg ␤ 3 -AR polymorphism and the lipoprotein lipase gene (Hϩ/Hϩ genotype) has been associated with a higher body mass index (Corella et al, 2001).…”

Thermoregulatory sympathetic nervous system activity and diet‐induced waist‐circumference reduction in obese Japanese women

“…This finding indicates that HRV power spectral analysis may provide a constructive and practical evaluation of energy metabolicand thermoregulatory sympathetic function in human. Taking the precursory national epidemic of metabolic syndrome into consideration, it would be challenging to explore whether VLF power, as a potential etiological indicator of obesity (Matsumoto et al, 1999(Matsumoto et al, , 2000(Matsumoto et al, , 2001(Matsumoto et al, , 2003Nagai et al, 2005Nagai et al, , 2006Shihara et al, 2001), is reversible through a suitable lifestyle modification.…”