Abstract
Interferon-gamma (IFNG) and its receptor (IFNGR1) are principal genes that associated with tuberculosis. In the current study we aimed to explore the genetic association of polymorphisms of IFNG and IFNGR1 with the risk of pulmonary tuberculosis (PTB) in the Chinese Tibetan population. We selected 467 PTB patients and 503 healthy controls to genotype 9 single nucleotide polymorphisms (SNPs). The unconditional logistic regression analysis was applied for assessing the associations, and the risk of PTB were evaluated by calculating the odds ratio (OR) and 95% confidence interval (CI). The results showed that mutants of rs9376268, rs1327475 and rs1327474 in IFNGR1 played a protective role in the PTB risk under genotype, dominant and additive model (P<0.05). On the contrary, minor allele “A” of rs2069705 in IFNG significantly increased the risk of PTB under genotype, dominant and additive model (P<0.05). However, after Bonferroni's multiple adjustment was applied to our data, which level of significant was set at P<0.0011 (0.05/45). Only variant of rs9376268 was significantly associated decrease the PTB susceptibility under additive model (OR=0.73, 95%CI=0.61-0.88, P<0.001). Furthermore, in the haplotype analysis, we found that the haplotypes “C-G-G-A-C”, “C-G-A-G-T” and “T-A-G-G-T” of rs9376267-rs9376268-rs1327475-rs7749390-rs1327474 block were extremely decreased the PTB risk (P<0.01), however, the haplotypes “C-G-G-A-T”, “T-G-G-G-T” and “C-G-G-G-T” of the block were extremely increased the PTB risk (P<0.01). These results suggested that variants of IFNGR1 may have a close relation with the PTB risk in Chinese Tibetan population.
Highlights
Tuberculosis (TB) remains to be a vital public health problem as well as leading cause of morbidity and mortality [1, 2]
In the haplotype analysis, we found that the haplotypes “C-GG-A-C”, “C-G-A-G-T” and “T-A-G-G-T” of rs9376267-rs9376268-rs1327475-rs7749390rs1327474 block were extremely decreased the pulmonary tuberculosis (PTB) risk (P
We used chi-square test to assess the influence of gene polymorphism of PTB risk in the allele model, and found that 3 single nucleotide polymorphisms (SNPs) in IFNGR1 significantly reduced PTB risk: rs9376268 (OR=0.73, 95%confidence interval (CI)=0.61-0.88, P=0.001), rs1327475 (OR=0.62, 95%CI=0.44-0.86, P=0.005) and rs1327474 (OR=0.54, 95%CI=0.35-0.84, P=0.006)
Summary
Tuberculosis (TB) remains to be a vital public health problem as well as leading cause of morbidity and mortality [1, 2]. Pulmonary tuberculosis (PTB), a pulmonary infectious diseases caused by Mycibacterium tuberculosis, which is the most common location, and the source of the infection is mainly through the respiratory tract. Epidemiological data showed that only about one-tenth of the population infected by Mycobacterium tuberculosis will develop clinical tuberculosis [4]. Twin study of Mycibacterium tuberculosis-infected individuals revealed that latently-infected monozygotic twins are more likely to develop pulmonary TB than latently infected dizygotic twins [5], and there are momentous racial differences in tuberculosis incidence. Study have indicated that genetic factors play an important role in the pathogenesis of tuberculosis [7]
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