维生素D及其受体基因遗传多态与结核病发病风险的关联研究

Vitamin D and polymorphisms of its receptor gene in association with the risk of tuberculosis

目的探讨血清维生素D水平及维生素D受体(vitamin D receptor,VDR)基因多态与结核病遗传易感性的关系。方法采用病例对照研究设计,病例来源于2008-2012年从江苏泰兴、镇江、武进、张家港、南京等地招募的活动性肺结核病人,共1 584例。对照组来自当地参加健康体检的居民,按年龄和性别与病例进行频数匹配,共1 566例。血清25-羟基维生素D的浓度检测采用艾狄斯TM25-羟基维生素D试剂盒,基因分型基于TaqMan分型技术。采用单因素和多因素Logistic回归模型计算比值比及其95%可信区间。结果病例组血清25-羟基维生素D浓度低于对照组,差异有统计学意义(Z=-11.28,P<0.001)。单位点分析发现,VDR基因上rs739837、rs757343和rs7975232位点基因多态与结核病的关联有统计学意义。与野生纯合子rs739837-GG基因型个体比较,携带变异纯合子TT基因型的个体患病风险下降约26%(调整OR=0.74,95%CI:0.55～0.99)。结论血清25-羟基维生素D水平及其代谢通路上的遗传多态与结核病的发病风险有关。

Objective To explore the serum vitamin D level and genetic polymorphisms of VDR gene in associa- tion with the susceptibility to tuberculosis. Methods A case-control study design was used. A total of 1 584 patients with active pulmonary tuberculosis were recruited from Taixing, Zhenjiang, Wujin, Zhangjiagang and Nanjing of Jiangsu from 2008 to 2012. 1 566 controls from a pool of individuals who participated in the local community-based health examination program were also recruited. Controls were frequency-matched to the cases by sex and age. Serum 25-hydroxyvitamin D concentration was measured by Aidisi 25-hydroxyvitamin D kit. Genotyping was performed by using TaqMan allelic discrim- ination technology. Univariate and multivariate logistic regression analysis were used to calculate odds ratio （OR） and 95% confidence interval （Cl）. Results Serum 25-hydroxyvitamin D concentration in cases was lower than that of controls. The difference was statistically significant （P 〈 0. 001 ）. Univariate analysis found that polymorphisms of rs739837, rs757343 and rs7975232 in VDR gene were significantly associated with the altered risk of tuberculosis. Compared with GG genotype of rs739837, the individuals carrying homozygous TT genotype had a 26% decreased risk （ adjusted OR = 0. 74, 95% CI： 0. 55-0. 99）. Conclusions Serum 25-hydroxyvitamin D concentration and genetic polymorphisms of vitamin D metabolic pathway genes are associated with the risk of tuberculosis.