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Background  Hypercholesterolemia 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.    Methods  We 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.    Results  We 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.    Conclusions  The 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.

The association of cholesterol absorption gene Numb polymorphism with Coronary Artery Disease among Han Chinese and Uighur Chinese in Xinjiang, China