| Tuberculosis(TB) is a kind of global infectious diseases caused by a single pathogennamed mycobacterium tuberculosis, and it is potentially lethal. According to the2013WHO report,1/3of the world’s population, about two billion people, are infected withTB at present, andincreases by eight million new annually at least, of which about1/3diedof TB. What’s more, multi-drug resistant tuberculosis (MDR-TB) has occurred amongnearly450thousand people, and finally,170thousand died of MDR-TB. Studies havefound that most individuals infected with mycobacterium tuberculosis will become apotentially infected person, which causes no symptom in a certain period of time. Inaddition to individual different nutrient levels and environmental factors, genetic factorsplays an important role in determining whether the tuberculosis attacks or not.PRDM1(also known as Blimp-1, located in human chromosome sixth), isa transcription factor which play important roles in a B cell developmentand differentiation, and it can also induce mature B lymphocyte developing into plasmacells and secreting antibodies so as to promote the immune response. Autophagy andapoptosis in macrophages is an important way of clearing mycobacterium tuberculosis invivo, and autophagy-related gene ATG5, as the conversion switch of autophagy andapoptosis, plays an important role in the regulation of occurrence and developmentof autophagy and apoptosis. ATG5is directly involved in two important links ofphospholipid bilayers extension and close of autophagic vacuoles, and the formation ofautophagic vesicles is the core process of autophagy occurrence. So far it is alsoan important marker for the detection and evaluation of autophagy. Recent studies alsoreported that PRDM1-ATG5gene variation can have an influence on the expression ofPRDM1and ATG5, thus affecting the immune response of the organism, therefore, wespeculate that PRDM1-ATG5gene polymorphism may be associated with tuberculosis infection.This study attempts to elucidate the relevance of gene polymorphism betweenPRDM1-ATG5rs548234site or rs6937876site and susceptibility to tuberculosis amongChinese Han population in the southwest area of China, in order to improve theprevention, diagnosis of tuberculosis, achieve TB risk prediction and lay a theoreticalfoundation for personalized medicine.The main contents and results:1. DNA was extracted successfully from the peripheral blood of251patients in casegroup and294healthy people in control group, genomic from, and its genotype rate reached100%identified by PCR sequencing.2. In this study, the distribution of genotypes of rs548234site and rs6937876sitein cases and controls were consistent with Hardy-Weinberg equilibrium law. Separateanalysis and conjoint analysis showed that there is no genetic association betweenrs548234site or rs6937876site and the risk of tuberculosis incidence.This study also found that there is no significant correlation between rs6937876siteand tuberculosis occurrence in primary pulmonary tuberculosis group and controlgroup; while there is a significant correlation between rs548234site and primarypulmonary tuberculosis, the frequency of CC genotype was higher than that in the healthycontrol group (CC vs. TT, OR=3.37，95%CI=1.498-7.579，p=0.003; CC vs CT+TT,OR=3.59,95%CI=1.642-7.848, p=0.001). After adjusting by smoking and townsdifferences, there were statistically significant differences of logistic regression analysis(OR=1.532,95%CI=1.238-2.076, P=0.03).Risk factors analysis showed that smoking and urbanization are the main risk factorsof tuberculosis (smoking vs. not smoking, OR=1.741,95%CI=1.189-2.547, p=0.004;OR=1.638, urban vs. not urban,95%CI=1.166-2.301, p=0.004), while other factors such asage, alcohol and occupations have no association with tuberculosis.In conclusion, the genotype distribution of rs548234site and rs6937876site inPRDM1-ATG5gene were consistent with Hardy-Weinberg equilibrium law. There isno genetic association between rs548234or rs6937876site and the risks of tuberculosis incidence in the entire population. However, the frequency of CC genotype in patients withprimary pulmonary tuberculosis was found higher than that in the healthy control group,suggesting that rs548234C allele may increase the risk of primary pulmonary tuberculosisincidence. The polymorphism of rs548234T/C may be involved in primary pulmonarytuberculosis of Han population in the southwest area of the China. |
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