Abstract
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.
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References
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 Med 168:928–935 (2008).
Gomes, F. et al. Obesity and coronary artery disease: role of vascular inflammation. Arq Bras Cardiol 94: 255–266 (2010).
Lorincz, A. M. & Sukumar, S. Molecular links between obesity and breast cancer. Endocr Relat Cancer 13:279–292 (2006).
Friedrich, M. J. Epidemic of obesity expands its spread to develo** countries. JAMA 287:1382–1386 (2002).
Pacheco, C. D. & Lieberman, A. P. The pathogenesis of Niemann-Pick type C disease: a role for autophagy? Expert Rev Mol Med 10:e26 (2008).
Lloyd-Evans, E. et al. Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat Med 14:1247–1255 (2008).
Kirchhoff, C., Osterhoff, C. & Young, L. Molecular cloning and characterization of HE1, a major secretory protein of the human epididymis. Biol Reprod 54:847–856 (1996).
Naureckiene, S. et al. Identification of HE1 as the second gene of Niemann-Pick C disease. Science 290: 2298–2301 (2000).
Friedland, N. et al. Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease. Proc Natl Acad Sci USA 100:2512–2517 (2003).
Storch, J. & Xu, Z. Niemann-Pick C2 (NPC2) and intracellular cholesterol trafficking. Biochim Biophys Acta 1791:671–679 (2009).
Barrett, J. C. Haploview: Visualization and analysis of SNP genotype data. CSH Protoc 10:71 (2009).
Kopelman, P. G. Obesity as a medical problem. Nature 404:635–643 (2000).
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. Circulation 113:898–918 (2006).
Haslam, D. W. & James, W. P. Obesity. Lancet 366: 1197–1209 (2005).
Selby, J. V. et al. Evidence of genetic influence on central body fat in middle-aged twins. Hum Biol 61: 179–194 (1989).
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 Health 63:651–658 (2009).
Cheung, C. Y. et al. Obesity susceptibility genetic variants identified from recent genome-wide association studies: implications in a chinese population. J Clin Endocrinol Metab 95:1395–1403 (2010).
Shastry, B. S. SNPs: impact on gene function and phenotype. Methods Mol Biol 578:3–22 (2009).
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).
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 Monit 16:CR180–185 (2010).
**, B. & Mi, J. FTO polymorphisms are associated with obesity but not with diabetes in East Asian populations: a meta-analysis. Biomed Environ Sci 22:449–457 (2009).
Liu, J. P. New functions of cholesterol binding proteins. Mol Cell Endocrinol 303:1–6 (2009).
Bi, X. & Liao, G. Cholesterol in Niemann-Pick type C disease. Subcell Biochem 51:319–335 (2010).
Blom, T. S. et al. Defective endocytic trafficking of NPC1 and NPC2 underlying infantile Niemann-Pick type C disease. Hum Mol Genet 12:257–272 (2003).
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Kim, S.K., Park, H.J., Lee, J.S. et al. Association of Niemann-Pick disease, type C2 (NPC2) polymorphisms with obesity in Korean population. Mol. Cell. Toxicol. 6, 391–396 (2010). https://doi.org/10.1007/s13273-010-0052-z
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DOI: https://doi.org/10.1007/s13273-010-0052-z