Department of Tuberculosis, Third Hospital of Zhenjiang City, Zhenjiang, China.
Int J Immunogenet. 2012 Jun;39(3):233-40. doi: 10.1111/j.1744-313X.2011.01079.x. Epub 2012 Jan 2.
A genome-wide association study (GWAS) of leprosy reported four specific genetic polymorphisms of NOD2 that were associated with susceptibility to Mycobacterium leprae in China. Considering the role of NOD2 in innate immune defence, we performed a study in a Chinese population to determine whether the same SNPs of NOD2 that were associated with disease caused by M. leprae were also associated with disease caused by Mycobacterium tuberculosis. We performed a frequency-matched case-control study in 1043 patients with pulmonary tuberculosis and 808 unaffected controls. All subjects were >15 years old and were Han Chinese from Jiangsu Province. We extracted DNA from a blood sample from each study participant. SNPs of rs3135499, rs7194886, rs8057341 and rs9302752 in the NOD2 gene were genotyped using a TaqMan-based allelic discrimination system. Using all possible patients with tuberculosis as cases, no significant association was found between the four specific SNPs and the risk of tuberculosis. In a subgroup analysis restricted to cases with bacteriologically confirmed tuberculosis (sputum culture positive), the variant genotype of rs7194886 was significantly associated with an altered risk of tuberculosis. Compared with the CC genotype, individuals carrying the CT/TT genotype of rs7194886 had an increased risk [odds ratio (OR) 1.35, 95% confidence interval (CI) (1.05-1.72)]. The association was stronger among tobacco smokers and males. By haplotype analysis, rs9302752C-rs7194886T was associated with an increased risk of bacteriologically confirmed tuberculosis (sputum culture positive) (P = 0.039), but it was not significant after correcting for multiple comparisons. In summary, genetic polymorphisms of the SNP rs7194886 in the NOD2 gene, which were discovered in the GWAS of leprosy, might also be associated with the pulmonary tuberculosis in the Chinese population.
一项针对麻风病的全基因组关联研究（GWAS）报告了 NOD2 基因的四个特定遗传多态性，这些多态性与中国人群中对麻风分枝杆菌的易感性有关。考虑到 NOD2 在先天免疫防御中的作用，我们在中国人群中进行了一项研究，以确定与麻风分枝杆菌引起的疾病相关的相同 NOD2 SNPs 是否也与结核分枝杆菌引起的疾病相关。我们在 1043 例肺结核患者和 808 例无影响对照中进行了频率匹配的病例对照研究。所有受试者年龄均> 15 岁，均为来自江苏省的汉族人。我们从每位研究参与者的血液样本中提取 DNA。使用 TaqMan 基于等位基因区分系统对 NOD2 基因中的 rs3135499、rs7194886、rs8057341 和 rs9302752 进行 SNP 分型。使用所有可能的肺结核患者作为病例，未发现这四个特定 SNPs 与结核病风险之间存在显著关联。在仅限于经细菌学证实的肺结核（痰培养阳性）的亚组分析中，rs7194886 的变异基因型与结核病风险改变显著相关。与 CC 基因型相比，携带 rs7194886 的 CT/TT 基因型的个体患结核病的风险增加[比值比（OR）1.35，95%置信区间（CI）（1.05-1.72）]。该关联在吸烟者和男性中更强。通过单体型分析，rs9302752C-rs7194886T 与经细菌学证实的肺结核（痰培养阳性）的风险增加相关（P = 0.039），但在多重比较校正后无统计学意义。总之，在麻风病 GWAS 中发现的 NOD2 基因 SNP rs7194886 的遗传多态性也可能与中国人群中的肺结核有关。
