Cholesterol homeostasis is essential for functional integrity of lipid. Niemann-Pick disease, type C2 (NPC2) encodes a protein containing a lipid recognition domain. NPC2 is related to regulation of cholesterol and other lipids. To evaluate NPC2 gene and its correlation to obesity in Korean population, 214 overweight/obese and 160 healthy control subjects were enrolled in this study. Genomic DNA was extracted from peripheral blood. Two tag single nucleotide polymorphisms (tag SNPs) in NPC2 gene were selected (rs8008540 and rs917394). Genotypes were determined using direct sequencing. For the analysis of genetic data, Helixtree software, SNPAnalyzer, SNPStats, and Haploview version 4.2 were used. Multiple logistic regression models (codominant, dominant, and recessive models) were performed for odds ratio (OR), 95% confidence interval (CI), and P value. In allele distribution analysis, allele of rs917394 was associated with obesity (OR=1.45, 95% CI=1.08–1.95, P=0.014). The genotype distributions of tag SNPs (rs8008540 and rs917394) were showed significant differences between overweight/obese and control subjects [rs8008540, OR=1.63, 95% CI=1.04–2.58, P=0.034 in codominant 1 (C/C versus C/T) model, OR=1.58, 95% CI=1.03–2.44, P=0.036 in dominant model; rs917394, OR=2.33, 95% CI=1.20–4.52, P= 0.013 in codominant model 2 (T/T versus C/C), OR= 1.62, 95% CI=1.05–2.52, P=0.030 in dominant model]. Haplotype (CT) was also associated with overweight/obese (frequency=0.589, chi square=6.100, P=0.014). These results indicate that NPC2 gene may be associated with obesity in Korean population.
Niemann-Pick disease type C2 (NPC2) Obesity Overweight Single nucleotide polymorphism Haplotype
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Burke, G. L. et al. The impact of obesity on cardiovascular disease risk factors and subclinical vascular disease: the Multi-Ethnic Study of Atherosclerosis. Arch Intern Med168:928–935 (2008).CrossRefPubMedGoogle Scholar
Gomes, F. et al. Obesity and coronary artery disease: role of vascular inflammation. Arq Bras Cardiol94: 255–266 (2010).CrossRefPubMedGoogle Scholar
Lorincz, A. M. & Sukumar, S. Molecular links between obesity and breast cancer. Endocr Relat Cancer13:279–292 (2006).CrossRefPubMedGoogle Scholar
Poirier, P. et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity and Metabolism. Circulation113:898–918 (2006).CrossRefPubMedGoogle Scholar
Selby, J. V. et al. Evidence of genetic influence on central body fat in middle-aged twins. Hum Biol61: 179–194 (1989).PubMedGoogle Scholar
Ortega-Alonso, A. et al. Genetic influences on adult body mass index followed over 29 years and their effects on late-life mobility: a study of twin sisters. J Epidemiol Community Health63:651–658 (2009).CrossRefPubMedGoogle Scholar
Cheung, C. Y. et al. Obesity susceptibility genetic variants identified from recent genome-wide association studies: implications in a chinese population. J Clin Endocrinol Metab95:1395–1403 (2010).CrossRefPubMedGoogle Scholar
Ben Ali, S. et al. The G3057A LEPR polymorphism is associated with obesity in Tunisian women. Nutr Metab Cardiovasc Dis [Epub ahead of print] (2010).Google Scholar
Jermendy, A. et al. Association between toll-like receptor polymorphisms and serum levels of tumor necrosis factor-alpha and its soluble receptors in obese children. Med Sci Monit16:CR180–185 (2010).PubMedGoogle Scholar
Xi, B. & Mi, J. FTO polymorphisms are associated with obesity but not with diabetes in East Asian populations: a meta-analysis. Biomed Environ Sci22:449–457 (2009).CrossRefPubMedGoogle Scholar