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目的探讨维生素D受体(VDR)基因TaqⅠ、FokⅠ位点基因多态性与宁夏回族自治区人群肺结核易患性之间的关系。方法搜集宁夏南部8个地区2010年7—11月确诊的肺结核患者993例(简称“病例组”),其中男550例,女443例;同期选择来源地区,与病例组性别相同、民族相同、年龄相当、居住环境相匹配的确认无肺结核的健康人880名(简称“对照组”),其中男485名,女395名。将聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测VDR基因多态性的方法,应用于人群结核病易感性的病例-对照研究。用SPSS 16.0软件对检测结果进行数据统计,各基因型与结核易感性关系用单因素分析和多因素logistic回归分析,以P<0.05为差异有统计学意义。结果VDR-TT、Tt、tt基因型在病例组和对照组中分布频率分别为83.0%(815/982)、15.2%(149/982)、1.8%(18/982)和84.7%(739/872)、14.7%(128/872)、0.6%(5/872),病例组与对照组差异有统计学意义(χ2=6.15,P=0.046)。VDR-FF、Ff、ff基因型病例组和对照组分布频率分别为32.4%(316/976)、47.9%(468/976)、19.7%(192/976)和28.5%(245/861)、53.3%(459/861)、18.2%(157/861),病例组和对照组分布差异无统计学意义(χ2=5.41,P=0.067)。在显性基因模型中,VDR-(TT+Tt)、tt基因型病例组和对照组中分布频率分别为98.2%(964/982)、1.8%(18/982)和99.4%(867/872)、0.6%(5/872),病例组和对照组中分布差异有统计学意义(χ2=5.98,P=0.014;OR=0.98、3.19,95%CI=0.978~0.997、1.193~8.574);在纯合基因模型中VDR-(FF+ff)、Ff基因型在病例组和对照组中频率分别为52.0%(508/976)、48.0%(468/976)和46.7%(402/861)、53.3%(459/861),病例组和对照组分布差异有统计学意义(χ2=5.27,P=0.022;OR=1.12、0.89,95%CI=1.023~1.298、0.822~0.985)。结论在宁夏人群中,肺结核易患性可能与VDR-TaqⅠ、FokⅠ位点多态性有关联,VDR-(FF+ff)、tt基因型可能是罹患肺结核的危险因素,而VDR-(TT+Tt)、Ff基因型可能是保护因素。
Objective To investigate the relationship between the gene polymorphisms of Taq Ⅰ and Fok Ⅰ of vitamin D receptor (VDR) gene and susceptibility to tuberculosis in Ningxia Hui Autonomous Region. Methods A total of 993 pulmonary tuberculosis patients (including “case group”) diagnosed from July to November in 2010 were collected from 8 districts in southern Ningxia. There were 550 males and 443 females. In the same period, 880 healthy people without tuberculosis (referred to as “control group”), of which 485 were males and 395 were females, with the same age and the same living environment. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) detection of VDR gene polymorphism method used in population-based case-control study of tuberculosis susceptibility. SPSS 16.0 software was used to test the data. The relationship between genotype and susceptibility to tuberculosis was analyzed by univariate analysis and multivariate logistic regression analysis. P <0.05 was considered statistically significant. Results The distribution frequencies of VDR-TT, Tt and tt genotypes were 83.0% (815/982), 15.2% (149/982), 1.8% (18/982) and 84.7% (739 / 872), 14.7% (128/872) and 0.6% (5/872) respectively. The difference between the case group and the control group was statistically significant (χ2 = 6.15, P = 0.046). The distribution frequencies of VDR-FF, Ff and ff genotype cases and control group were 32.4% (316/976), 47.9% (468/976), 19.7% (192/976) and 28.5% (245/861), respectively 53.3% (459/861) and 18.2% (157/861) respectively. There was no significant difference in the distribution between case and control group (χ2 = 5.41, P = 0.067). In the dominant gene model, the distribution frequencies of VDR- (TT + Tt), tt genotype cases and controls were 98.2% (964/982), 1.8% (18/982) and 99.4% (867/872) ) And 0.6% (5/872) respectively. There was significant difference between the case group and the control group (χ2 = 5.98, P = 0.014; OR = 0.98, 3.19, 95% CI = 0.978-0.997, In the homozygous model, the frequencies of VDR- (FF + ff) and Ff genotypes were 52.0% (508/976), 48.0% (468/976) and 46.7% (402/861) in the case and control groups, respectively , 53.3% (459/861) respectively. There was significant difference in the distribution between case group and control group (χ2 = 5.27, P = 0.022; OR = 1.12,0.89,95% CI = 1.023-1.298, 0.822-0.985). Conclusions In Ningxia population, the susceptibility to tuberculosis may be related to the VDR-TaqⅠand FokⅠ polymorphisms. The VDR- (FF + ff) and tt genotypes may be the risk factors of tuberculosis. VDR- (TT + Tf), Ff genotype may be a protective factor.