| Background and Objective: China’s current TB epidemic is still very serious, the rate of AIDS infection has increased year by year, the merger of the two infection increased significantly, the tuberculosis or AIDS treatment and control are more difficult, which can lead to higher risk of death. Therefore, the high-risk groups of HIV infection in early screening and at the same time in the HIV infected TB screening, early treatment,improve the prognosis and to provide scientific basis for prevention and control of tuberculosis infection effectively and merged with HIV infection. However, the epidemic of tuberculosis prevention and treatment of more serious is the growing number of resistant strains of tuberculosis, tuberculosis incidence has increased year by year, a serious threat to people’s health; therefore, investigation and analysis on the development of drug resistance distribution in Xinjiang area is very important. Preliminary scientific research shows that TB drug resistance and gene mutation related to understand the molecular mechanism of drug resistance of Mycobacterium tuberculosis, from gene level,conducive to the establishment of a sensitive method to detect a specific treatment for tuberculosis infection, screening and screening of resistant patients; especially by environmental factors, resistant strains of Mycobacterium tuberculosis in different regions of the gene mutation may there is a big difference. Therefore, the research of Mycobacterium tuberculosis resistant gene mutation of Mycobacterium tuberculosis in a region and the gene mutation, to investigate the cytokine induced SRC homology 2domain protein(Cytokine-inducible SRC homology 2(SH2) domain, protein, CISH) on the susceptibility of tuberculosis infection, to understand the effect of CISH gene polymorphism in the pathogenesis of tuberculosis of Uighur population in Xinjiang area,it can provide a scientific basis for effective prevention and control of tuberculosis.Methods: Using cross-sectional survey method and Relying on the analysis on the epidemiological characteristics and risk factors of TB/HIV infected patients in Xinjiang, it was to understand the infection of TB with HIV in the western region of minority population. Using the molecular epidemiology method, Positive strains of tubercle bacillus with the rapid culture registered in four districts of Urumqi from 2012 to 2013 were collected. The drug sensitivity test was performed on strains, as well as the analysis on the drug resistance. Observed the distribution of drug-resistant strains of TB among initially-treated and retreated patients. The modified Jensen medium proportion method was employed to calculate the drug-resistant percentage of strains, gene sequencingmethod for the sequencing. Gene Align of Lasergene was adopted to compare the sequencing results and the gene sequence of standard H37 Rv to confirm the locus of gene mutation. Using Methods of case-control study, CISH gene SNP was selected by Haploview, Snap Shot method was used for the genetic polymorphism detection to understand the effect of gene polymorphism of CISH gene of Uygur people on the incidence of TB and SNPs haplotype was constructed.Results:1. The research registered a total of 3657 cases of TB, and detected 2645 cases of HIV antibody. The detection rate of HIV antibody was 72.3%. 128 cases were HIV antibody positive, and the positive inspection rate was 4.8%. The influence factor analysis showed that: the risk of TB patients infecting HIV who were 35 years old or older than 35 years old was 0.26 times(95%CI: 0.18-0.40) higher than that of 18-35 years old patients,and the risk of infecting HIV in sputum smear positive patients with pulmonary tuberculosis and extra pulmonary tuberculosis was separately 0.43 times(95%CI:0.28-0.66) and 1.79 times(95%CI: 1.09-2.94) higher than that of sputum smear negative patients. The research registered a total of 2714 cases of HIV infectors / AIDS patients,and 1284 cases were followed up in which 1195 cases were performed TB screening.The screening rate was 93.1%. 91 cases of TB infection were found, and the infection rate was 7.6%. The influence factor analysis showed that: the risk of male HIV infectors/AIDS patients infecting TB was 12.2 times(95%CI: 6.4-23.1) higher than that of female,and the risk of HIV infectors/AIDS patients infecting TB whose CD4 cell number was equal to or less than 200 was 20.4 times(95%CI: 11.8-35.3) higher than that of patients whose CD4 cell number was more than 200. 2. Except the drug resistance rate of tubercle bacillus to amikacin lower than 20%, the one to other first-line and second-line anti-TB drugs was all higher than 30%. In addition, the drug resistance of tubercle bacillus for retreated patients was significantly higher than the one for the initially-treated patients.The drug resistance rate to the first-line anti-TB drugs was 54.9%, where the one for the initially-treated patients was 35.7% and the one for the retreated patients was 81.6%.Among 4 first-line anti-TB drugs, the drug resistance rate to isonicid was highest as46.1%, while the one to ethambutol was lowest as 26.8%. The drug resistance rate to the second-line anti-TB drugs was 46.1%, where the one for the initially-treated patients was33.3% and the one for the retreated patients was 64.3%. Among three second-line anti-TB drugs, the drug resistance rate to ofloxacin was highest as 36.7%, while the one to amikacin was lowest as 16.2%.3. The mutation rate of rpo B gene was 59.77%. Mutation range from 505 codon to 572 codon, which had a total of 11 loci and 14 types. 1 of the 52mutant strains had double mutation in codon CAC-TGC, and the rest were codon mutation.Mutation of the point gene and combination mutation of two codon were existed.There were 52 mutation strains, included the mutant strain of 44(84.6%).Mutation codon505, 516,526, 531, 533 codon mutation were most common. The mutation of the 526 codon is the second place.The remaining eight strains of tuberculosis were combined mutations of the two codon.There were 18 mutant strains that had kat G or inh A mutations,or both of them were mutated simultaneously. 4. Compared with the healthy control group,CISH gene polymorphism sites rs17051025 in tuberculosis group in the A allele frequency higher than control group(P<0.05), frequency of AA genotype in tuberculosis group is higher than that of healthy control group(P<0.05). Compared with the healthy control group, the CISH gene polymorphism site rs2239751 was higher in the tuberculosis group(P<0.05), there were 6 major haplotypes. The frequency of three haplotypes(TCCG, ACAG and TCAG) was less than 5% and thus the statistics was not performed on them. There was no significant different in the frequency of other three haplotypes between two groups.Conclusions: The infection rate of TB with HIV is high in Xinjiang. Persons over 35year-old with the smear positive/extrapulmonary TB and male HIV-infected/AIDS patients with CD4 cells ≤200 are high-risk groups, which require the double screening of TB/HIV. The drug resistance rate of tubercle bacillus to the first-line and second-line anti-TB drugs in Xinjiang is relatively high. Most of mutation types of drug-resistant gene of tubercle bacillus in Xinjiang is consistent with the findings of previous researches.SNPs in CISH gene of Uyghur people are related to the susceptibility of tuberculosis,while rs17051025 and rs2239751 of 4 polymorphic loci are risk factors. Recommended the strengthening of China’s western frontier minority areas TB and HIV and resistance of the prevention and control work, especially to explore the importance of TB complicated with HIV infection and the molecular mechanism of drug resistance tuberculosis. |
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