关键词: 结核, 肺/遗传学, 受体, 骨化三醇, 多态性, 单核苷酸, 疾病遗传易感性, 病例对照研究, 宁夏［回族自治区］

Abstract: Objective This study aimed to explore the relationship between SNP polymorphisms in TaqⅠand FokⅠ in the Vitamin D Receptor (VDR) gene and susceptibility to pulmonary tuberculosis (PTB) among the populations in Ningxia Hui Autonomous Region (NHAR), P.R. of China. Methods The confirmed 993 PTB cases (550 males and 443 females) were recruited in different TB clinics of southern NHAR in 2010, who had been diagnosed according to WHO TB-diagnosis criteria, without any other co-infections. The 880 healthy matched controls, including 485 males and 395 females were recruited to match the sex, nationality, age and residential area of the TB cases. The detection of two SNPs (TaqⅠ, FokⅠ) in the VDR gene was demonstrated by use of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. All data were entered into the SPSS 16.0 software package. The population data were tested by the Hardy-Weinberg method and then multiple logistic regression models were used for further investigation of the risk gene SNPs in different genetic models, and included covariates that had shown association with disease in the univariate analysis. The significance value was determined within 95% confidential intervals with P<0.05. Results The genotype frequencies of VDR-TT, Tt and tt were 83.0%(815/982), 15.2%(149/982), 1.8%(18/982) and 84.7%(739/872), 14.7%(128/872), 0.6%(5/872) in the case and control groups, respectively, with significant difference (χ²=6.15, P=0.046). The genotype frequencies of VDR-FF, Ff and ff were 32.4%(316/976), 47.9%(468/976), 19.7%(192/976) and 28.5%(245/861), 53.3%(459/861), 18.2%(157/861) in the case and control groups, respectively, without any significant differences between the case and control groups. The genotype frequencies in the dominant model of VDR-(TT+Tt), tt were 98.2%(964/982), 1.8% (18/982) and 99.4% (867/872), 0.6 (5/872) in the case and control groups with significantly different value (χ²=5.98, P=0.014) and an OR(95%CI) of 0.98,3.19(0.978-0.997, 1.193-8.574). The genotype frequencies in the heterozygote model of VDR-(FF+ff), Ff were 52.0%(508/976), 48.0%(468/976) and 46.7%(402/861), 53.3%(459/861) in cases and controls, with significant value (χ²=5.27, P=0.022) and an OR(95% CI) of 1.12,3.19(1.023-1.298, 0.822-0.985). Conclusion The VDR TaqⅠand FokⅠpolymorphism was associated with susceptibility to human pulmonary tuberculosis amongst Ningxia Populations. The genotype of the VDR-(FF+ff), tt showed a potential association with risk factors to human pulmonary tuberculosis in the study population groups. The genotypes of the VDR-(TT+Tt) and Ff may be associated with increased resistance to disease.

Key words: Tuberculosis, pulmonary/genetics, Receptors, calcitriol, Polymorphism, single nucleotide, Genetic predisposition to disease, Case-control studies, Ningxia