Abstract
Purpose
It is important to identify a ‘metabolically unhealthy obese’ subset with higher cardiovascular risk among obese individuals. We investigated the associations between the GNB3 C825T polymorphism and obesity-related metabolic risk factors among Korean obese women.
Methods
This study was a sub-investigation of a double-blind randomized controlled trial that examined the additive effect of or list at on weight loss with sibutramine. A sample of 111 obese women were divided into T-carriers (CT/TT) or a homozygous CC group, according to the presence of the 825T allele at GNB3. These groups were compared to determine their associations with obesity-related metabolic risk factors, i.e., fasting plasma glucose, serum lipids, serum insulin/insulin resistance, and abdominal fat amounts.
Results
The allele frequencies of the GNB3 polymorphism were C allele = 59.5 % and T allele = 40.5 %. The T allele was found to be significantly associated with greater visceral fat and higher serum lipids, and these significances remained robust after adjusting for potential covariates.
Conclusions
The GNB3 825T polymorphism is significantly associated with greater visceral fat and higher serum lipids in Korean obese women and it suggests that the GNB3 C825T is a determinant of obesity-related metabolic traits in this population.
Abbreviations
- WC:
-
Waist circumference
- SNP:
-
Single nucleotide polymorphism
- GNB3:
-
Guanine nucleotide-binding protein beta 3 subunit
- BMI:
-
Body mass index
- TG:
-
Triglyceride
- CT:
-
Computed tomography
- LDL-C:
-
Low-density lipoprotein cholesterol
- PCR:
-
Polymerase chain reaction
References
Sims EA (2001) Are there persons who are obese, but metabolically healthy? Metabolism 50:1499–1504
Ortega FB, Lee DC, Katzmarzyk PT et al (2013) The intriguing metabolically healthy but obese phenotype: cardiovascular prognosis and role of fitness. Eur Heart J34:389–397
Padwal RS, Pajewski NM, Allison DB, Sharma AM (2011) Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity. CMAJ 183:1059–1066
Joy T, Lahiry P, Pollex RL, Hegele RA (2008) Genetics of metabolic syndrome. Curr Diab Rep 8:141–148
Regard JB, Sato IT, Coughlin SR (2008) Anatomical profiling of G protein-coupled receptor expression. Cell 135:561–571
Hsiao TJ, Hwang Y, Liu CH, Chang HM, Lin E (2013) Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population. Genes Nutr 8:137–144
Wascher TC, Paulweber B, Malaimare L et al (2003) Associations of a human G protein Beta3 subunit dimorphism with insulin resistance and carotid atherosclerosis. Stroke 34:605–609
Nürnberger J, Dammer S, Philipp T, Wenzel RR, Schafers RF (2003) Metabolic and haemodynamic effects of oral glucose loading in young healthy men carrying the 825T-allele of the G protein β3 subunit. Cardiovasc Diabetol 2:7
Hwang IC, Park JY, Ahn HY et al (2014) Effects of CYP3A5, CYP2C19, and CYP2B6 on the clinical efficacy and adverse outcomes of sibutramine therapy: a crucial role for the CYP2B6*6 allele. Clin Chim Acta 428:77–81
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419
Lee JY, Kim SU, Cho JK, Woo SK, Kang HS (2009) GNB3 C825T polymorphism and elevated blood pressure. Int J Sports Med 30:892–897
Arner P (1999) Catecholamine-induced lipolysis in obesity. Int J Obes Relat Metab Disord 23 Suppl 1:10–13
Ryden M, Faulds G, Hoffstedt J, Wennlund A, Arner P (2002) Effect of the (C825T) Gbeta(3) polymorphism on adrenoceptor-mediated lipolysis in human fat cells. Diabetes 51:1601–1608
Jocken JW, Blaak EE, Schiffelers S (2007) Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation. Int J Obes (Lond) 31:813–819
NicholsonAC HajjarDP (1992) Transforming growth factor-beta up-regulates low density lipoprotein receptor-mediated cholesterol metabolism in vascular smooth muscle cells. J Biol Chem 267:25982–25987
VijayagopalP SrinivasanSR, RadhakrishnamurthyB Berenson GS (1991) Studies on the mechanism of uptake of low density lipoprotein-proteoglycan complex in macrophages. Biochem Biophys Acta 1092:291–297
Ishikawa K, Imai Y, Katsuya T et al (2000) Human G-protein beta3 subunit variant is associated with serum potassium and total cholesterol levels but not with blood pressure. Am J Hypertens 13:140–145
Andersen G, Overgaard J, Albrechtsen A et al (2006) Studies of the association of the GNB3 825C > T poly-morphism with components of the metabolic syndrome in white Danes. Diabetologia 49:75–82
Stefan N, Stumvoll M, Machicao F et al (2004) C825T polymorphism of the G protein beta3 subunit is associated with obesity but not with insulin sensitivity. Obes Res 12:679–683
Acknowledgments
The original clinical trial (NCT01184560) was funded by Hanmi Pharmaceuticals, Ltd., Seoul, Korea.
Conflict of interest
The authors have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
K. D. Ko and K. K. Kim contributed equally to this work.
Rights and permissions
About this article
Cite this article
Ko, K.D., Kim, K.K., Suh, H.S. et al. Associations between the GNB3 C825T polymorphism and obesity-related metabolic risk factors in Korean obese women. J Endocrinol Invest 37, 1117–1120 (2014). https://doi.org/10.1007/s40618-014-0182-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40618-014-0182-6