Association of Niemann-Pick disease, type C2 (NPC2) polymorphisms with obesity in Korean population

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.

Exacerbating and reversing lysosomal storage diseases: from yeast to humans

“…In European populations, a GWAS identified three new alleles of NPC1 strongly associated with obesity 154 . Similarly variation at the NPC2 locus has been associated with obesity in Korean populations 155 . These observations have subsequently been recapitulated in several animal models of NP-C disease 156 157 .…”

Polymorphisms of IGFI contribute to the development of ischemic stroke

“…Hardy-Weinberg equilibrium (HWE) was calculated using the Chi-square test. Multiple logistic regression models were conducted using the following models: codominant1 (major allele homozygotes vs. heterozygotes), codominant2 (major allele homozygotes vs. minor allele homozygotes), dominant (major allele homozygotes vs. heterozygotes and minor allele homozygotes), recessive (major allele homozygotes and heterozygotes vs. minor allele homozygotes) and log-additive (major allele homozygotes vs. heterozygotes vs. minor allele homozygotes) (16,17). Bonferroni correction was performed to obtain further statistical significance.…”