Study On The Association Between Genetic Expression And Single Nucleotide Polymorphism And Tuberculosis Susceptibility In Mongolian

Tuberculosis(TB)is a major global health threat caused by Mycobacterium Tuberculosis(Mtb).In China epidemiological studies have shown that TB epidemic of ethnic minorities is higher than that of the Han nationality,Mongolian,in particular has much higher TB incidence than Han,indicating that genetic factors may affect the TB susceptibility,especially the Mongolian and other ethnic minorities in our country.Currently,reduction of the TB epidemic in ethnic minorities is a big challenge due to the lack of scientific information on the genetic susceptibility of TB in Monglian and other ethnic minorities,understanding of the TB susceptibility of Mongolian will provide critical information for the generation of effective strategy for better prevention and control of TB in the ethnic minorities in China.Based on the case-control study design,the correlation between genetic polymorphism of TB susceptibility associated genes ASAP1,NRAMP1,SP110,TLR2 and TLR4 in Mongolian TB patients and healthy controls was performed in this study.1.Basic information collection and specimen collection of the research object.According to the "Health Industry Standard TB Diagnostic Criteria of the People’s Republic of China(WS 288-2017)",blood samples of Mongolian and local Han TB populations and healthy controls in Inner Mongolia autonomous region were collected with the patient’s knowledge and consent and Ethics Review by Institutional Ethics Review Committee of Shanxi University.Blood samples of a total of 414 cases of Mongolian and 131 cases of Han were collected,of those samples,197 samples from Mongolian TB cases,217 samples from healthy Mongolian health volunteers,56 samples from Han Tb cases and 75 cases of healthy control.All subjects voluntarily participated in the study and filled in the informed consent.Chi-square testand SAS9.1GLM proved that there were no significant differences in gender,age,smoking,drinking and tuberculosis susceptibility between Mongolian and Han.2.Correlation analysis of ASAP1,NRAMP1 and SP110 gene expression levels and TB susceptibility in Mongolian and Han ethnic groups.With the case-control study design,quantification of TB associated gene m RNA expression of blood samples collected from both Mongolian and Han in the Inner Mongolia Autonomous Region was performed using real-time fluorescent quantitative PCR.We tested blood samples of 96 patients and 126 health control from Mongolian and analyzed the m RNA expression difference of ASAP1,NRAMP1 and SP110 m RNA between Han and Mongolian.The results showed that Mongolian ethnic group with higher m RNA levels in ASAP1 and NRAMP1 were more susceptible to TB compared to the counterparts(P < 0.05).Meanwhile,the expression levels of SP110 in Mongolian female TB patients was significantly different(P < 0.05)contrast with those in healthy population.In Han ethnic group,it was observed that higher m RNA levels of NRAMP1 in TB patients than those in the control group were statistically significant(P < 0.05),however,no significant difference between TB patients and healthy group with the respect to ASAP1 and SP110 m RNA.The data given in our studies indicated that the TB susceptibility of Mongolian and Han nationalities is related to the expressions of host genes ASAP1,NRAMP1 and SP110.3.Correlation analysis between single nucleotide polymorphism of TB susceptibility associated genes in Mongolian.Twenty-six SNPs selected from ASAP1,SP110,NRAMP1,TLR2 and TLR4 in venous blood samples were detected by real time PCR technique.The results showed that rs10956514,rs4733781,rs2033059,rs1017281,rs1469288 and rs17285138 selected by ASAP1 had no significant differences between Mongolian TB and healthy controls,so we conclude that ASAP1 was not colltcted with Mongolian TB susceptibility in the current sample size.Analysis of the 3 ’UTR(rs17235416),INT4(rs3731865)and rs2276631 of NRAMP1 showed no significant difference between TB patients and health control of Mongolian neither due to sample size probably.Allele A of D543N(rs17235409)may related with the higher risk of TB by comparison with the allele G.No significant differences were found in SNPs rs1135791,rs1365776 and rs11556887 in SP110 polymorphisms in the tested samples of between Mongolian TB and healthy controls.Analyses of SNPs in SP110 showed that rs9061 T/C,rs722555 C/T,rs3948464 G/A and rs11679983 A/G were correlated with the higher risk TB in Mongolian,showing there SNPs are associated with TB susceptibility.SPNs rs3804100 C/T and rs3804099C/T in TLR2,and SNPs rs11536889 C/T,rs10759932 C/T and rs10759931A/G might have higher risk of TB incidence in Mongolian.The above studies showed that the population both in Mongolia ethnicity and Han ethnicity had different susceptibility to TB due to the gene mutation and varied expressions in ASAP1,NRAMP1 and SP110 and others(NRAMP1gene D543N(rs17235409),SP110 gene rs9061,rs722555,rs3948464,rs11679983,TLR2rs3804100,rs3804099,TLR4 rs11536889,rs10759932,rs10759931).This finding indicated that persons who are at high risk with tuberculosis could be screened based on these genetic mutations and their expression variations.Thereby,the measures could be taken to prevent the incidence of tuberculosis and control the mortality by early diagnosis and early treatment among these high-risk populations,particularly in Mongolia.