Genetic polymorphisms of nucleotide binding oligomerization domain 2 gene and the risk of pulmonary tuberculosis / 中华传染病杂志

ABSTRACT

Objective To validate the association between genetic polymorphisms of nucleotide binding oligomerization domain 2 (NOD2) gene and the risk of tuberculosis in Chinese population.Methods A validation case-control study was performed with a total of 1043 pulmonary tuberculosis patients and 808 healthy controls.All controls had no history of tuberculosis or malignancy,and were matched with cases by sex and age.Genomic DNA from the peripheral blood samples of participant was extracted.Single nucleoside polymorphisms (SNP) of rs3135499,rs7194886,rs8057341,and rs9302752 in the NOD2 gene were genotyped using a TaqMan-based allelic discrimination system.The chi-square test was used to analyze categorical data and Logistic regression model was used to calculate the odds ratio (OR) and 95％ confidence interval (CI).Results When all patients as the cases were included in the analysis,no significant association was found between the four SNP of NOD2 gene and the risk of pulmonary tuberculosis.In a subgroup analysis by restricting cases to sputum culture positive patients,the variant genotypes of rs7194886 were 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 (OR =1.35,95％ CI1.05-1.72) for sputum culture positive tuberculosis.After adjusted for potential confounders,the increased risk of CT/TT genotype was still observed (OR=1.35,95％CI1.05-1.73).Stratification analysis revealed that the effect of the SNP rs7194886 (CT/TT vs TT) was significant among men (OR=1.44,95％CI1.08-1.92),individuals with age ＜55 years (OR=1.51,95％CI1.05-2.16),smokers (OR=1.53,95％CI1.07-2.18),and alcohol drinkers (OR=1.84,95％CI1.01-3.33).But the heterogeneity test was not significant.Haplotype analysis showed that the rs9302752C-rs7194886T haplotype was associated with an increased risk of sputum culture positive tuberculosis (x2 =4.27,P=0.039).Conclusion In summary,genetic polymorphisms of rs7194886 in the NOD2 gene may be associated with the risk of pulmonary tuberculosis in the Chinese population.