Abstract
BackgroundHypercholesterolemia is a major risk factor for coronary artery disease (CAD). As Numb is an important regulating factor for intestinal cholesterol absorption and plasma cholesterol level, the aim of the present study is to assess the association between human Numb gene polymorphism and CAD among Han and Uighur Chinese.MethodsWe have conducted two independent case–control studies in Han Chinese (384 CAD patients and 433 controls) and Uighur Chinese (506 CAD patients and 351 controls) subjects. All subjects were genotyped for four kinds of SNPs (rs12435797, rs2108552, rs1019075 and rs17781919) and SNP is used as a genetic marker for human Numb gene. Genotyping was undertaken using TaqMan SNP genotyping assay, and the subjects’ ethnicity and gender were considered in the analysis.ResultsWe found that rs2108552 was associated with CAD in the dominant model (CC vs CG + GG) for the total Han Chinese population (n = 200) and Han Chinese males (n = 115) (P = 0.004 and P = 0.001, respectively). The difference remained statistically significant after multivariate adjustment (total: OR = 1.687, P = 0.004; male: OR = 1.498, P = 0.006). Further, for the total (n = 817) and male (n = 490) Han Chinese, the frequency of the haplotype (T-C-T-C) was significantly higher in the CAD patients than in the controls (P = 0.004 and P = 0.002), and the frequency of the haplotype (G-G-T-C) was significantly lower in the CAD patients than in the control subjects (P = 0.013, P = 0.007). In addition, for the total (n = 857) and male (n = 582) Uighur Chinese, we observed that rs12435797 was associated with CAD in an additive and recessive model (P = 0.021 and P = 0.009; P = 0.048 and P = 0.034). However, the difference did not remain statistically significant after multivariate adjustment. The overall distribution of rs2108552, rs1019075 and rs17781919 genotypes, alleles and the frequency of the haplotype established by four SNPs showed no significant difference between CAD patients and control subjects in the total, male and female Uighur Chinese.ConclusionsThe results of this study indicate that CC genotype of rs2108552 and T-C-T-C haplotypes in Numb gene is a possible risk genetic marker and G allele and G-G-T-C haplotypes is a possible protective genetic marker for CAD in male Han Chinese.
Highlights
Cholesterol is an important structural component of cell membranes, and a precursor for bile acids, vitamin D, and steroid hormone [1]
All information and data regarding essential hypertension (EH), diabetes mellitus (DM), hyperlipidemia and smoking were collected from all study subjects, and they were matched between two coronary artery disease (CAD) and control cohorts individually
We have found two haplotypes (T-C-T-C and G-G-T-C) of SNP1-SNP2-SNP3SNP4 in Han male Chinese and assumed that the haplotype (T-C-T-C) is a risk factor for CAD and G-G-T-C is a protective factor for in Chinese Han male population according to the logistic regression and haplotype analyses
Summary
Cholesterol is an important structural component of cell membranes, and a precursor for bile acids, vitamin D, and steroid hormone [1]. Pei Shan Li et al [20] has revealed that there exists an interaction between clathrin adaptor Numb and NPC1L1 during the regulation of cholesterol absorption. They have found that Numb recognizes the particular endocytic motif (YVNXXF) in C-terminal of NPC1L1, finishes the internalization by recruiting clathrin/AP2, and transports cholesterol to endocytic recycling compartment (ERC) through microfilaments. As Numb is an important regulating factor for intestinal cholesterol absorption and plasma cholesterol level, the aim of the present study is to assess the association between human Numb gene polymorphism and CAD among Han and Uighur Chinese
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