Study On The Relationship Between NRAMP1 And MBL Gene Polymorphisms And Susceptibility To Tuberculosis In Qinghai

Objectives:(1)To study the relationship between the tuberculosis with NRAMP1 and MBL gene polymorphisms in Qinghai area;(2)To further understand the MBL level of tuberculosis patients in Qinghai area,and to explore the relationship between MBL level and tuberculosis.Methods:(1)A case-control study was conducted in 262 tuberculosis patients from the fourth People’s Hospital of Qinghai province and 256 healthy people matched to the PTB patients based on the age,gender,place of residence were collected as control group.PCR-RFLP technology was used to detect the genotypes of3’UTR,D543 N,INT4 of NRAMP1 and AB,AC,AD loci of MBL,and the PCR-SSP technology was used to study the genotypes of HL and PQ loci of MBL.P-value and odds ratios were calculated to evaluate the associations between NRAMP1 and MBL gene polymorphisms and tuberculosis in Qinghai.(2)253 patients with PTB and 241 healthy controls matched with the age,sex and place of residence with the tuberculosis group were collected from the Fourth People’s Hospital of Qinghai Province.Enzyme-linked immunosorbent assay(ELISA)was used to detect plasma MBL levels between the two groups,and to explore the relationship between plasma MBL concentration and pulmonary tuberculosis.Combined with the genotypes measured above,further analyze the relationship between plasma MBL level and SNPs.Results:(1)There was mutation at the 3’UTR site,among which the TGTG/del genotype frequency was higher in the tuberculosis group,and the distribution of the three genotypes was different between the two groups(P=0.007),and the del allele frequency is higher in the PTB group(P=0.001).The distribution of homozygous AA genotype at the D543 N locus was not found in either group,the frequencies of GG genotype were 87.40% and 92.97% in the tuberculosis group and the control group,respectively,and the GA genotype accounted for 12.60% in the tuberculosis group,which was higher than that of the control group 7.03%(P<0.05),the A allele frequency was higher in the PTB group(P<0.05).The frequencies of the three genotypes at the AB locus were different between the two groups(P<0.05),the frequency of B allele in the PTB group was higher than that in the control group(P=0.007).Distributions of PP,PQ and QQ genotypes in two groups were different(P=0.001),the frequencies of the two groups were 91.98%,6.49%,1.53% and80.86%,14.84%,4.30%,respectively,the P allele frequencies were higher in the PTB group(P=0.0001).There was no difference in polymorphism between INT4 and HL loci(P>0.05).(2)By t-test,the plasma MBL level of tuberculosis patients was significantly lower than that of the control group(P=0.001),we also found that the expression levels of different genotype groups were different,the tuberculosis patients with BB genotype had the lowest MBL concentration,and those with AA genotype were the highest,and the difference was significant(P<0.05).Conclusions:(1)NRAMP1 gene 3’UTR,D543 N and MBL gene AB,PQ polymorphisms may be related to the pulmonary tuberculosis in Qinghai;and NRAMP1 gene 3’UTR-del,D543N-A and MBL genes AB-B,PQ-P allele may be risk factors to tuberculosis in Qinghai.(2)The plasma MBL concentration of tuberculosis patients is significantly lower than that of healthy controls,and the plasma MBL concentration of participants carrying AA genotype is the highest.