A Study On The Association Of DNA Polymorphisms Of NRAMP1 Gene With Susceptibility To Tuberculosis In Hainan Li Ethnic Population

ObjectiveTuberculosis(TB)is one of the major infections diseases in the human health,which is also a major killer of human health since ancient times.Mycobacterium tubercubosis in fection in the population is only one tenth of the incidence,suggesting that individual differences in susceptibility may be related to TB.TB in the past mainly focused on bacteria and environmental factors on the incidence and impact.With the development of genomic edidemiology,host susceptibility gene in the development of disease,and increasing the role of people's attention.Naturally,the natural resistance associtted macrophage protein1(NRAMP1)gene is a key candidate susceptibility gene.The host of different genotype may affect the resistance of Mycobacterium tuberculosis.TB case control study conducted by reseach findings in Afrian indicate that NRAMP1 gene polymorphisms related the incidence of tuberculosis,and there are ethnic differences in genotype frequencies. Hai nan has conducted similar studies for the domestic,and 80%of TB patients in the rural areas,which are mainly located in poor areas.Li ethnic population is the only minority of Chinese 55 minority nationalities in Hainan Province.Hainan Li ethnic population studies have found sputum smear positive rate was 13.1%,9.9% higher than the average level of other cities in Chinese Hai nan population.The current study is about D543N and 3'UTR polymorphic loci.China has a large number of population,which is a multy ethnic country.Li ethnic population has not yet been reported in literature.This research was about NRAMP1 gene polymorphism in the DNA of different region and nation in China and the distribution of genotypes.To carry out in depth study that will help further understanding of the pathogenesis of TB and ether mycobaterial infections,in order to promote the improvement of the treatment plan.MethodsCase control study design was adopted.PCR-RELP techniqnes were used to type NRAMPI gene pdymorplvisms(D543N and 3'UTR)among 130 patients with active TB and 225 health individuals. Informations on related questionnaire.The relationship of D543N and 3'UTR polymorphism and susceptibility to TB were studied,and case were grouped according to genotype.Results1.Case compared with the control group in generalA total of 130 well defined TB patients and 223 unrelated normal controls were recruited for the study. Case group,aged form 18 to 76 years old,with an average age of 47,control group,aged from 20 to 78 years old,with an average age of 49.Through statistical analysis,there is no significant defference of case and control groups in age,place of birth,marital status,etc.2.Enviromental and gender-related factor analysisFactors related to TB,which found in cases and the control group,the distribution of sex and alcohol are significant differences.OR is 3.937(2.459-6.304)and 2.435 (1.507-3.937),(p＜0.0001)3.D543N and 3'UTR polymorphisms of NRAMPI gene associated with the univariate factor analysis of TB.The univariate factor analysis show 3'UTR TGTG-/TGTG-genotype frequencies and 3'UTR TGTG+/TGTG-genotype frequencies signinficantly higher in patients,OR is 5.531 (2.649-11.549)and0.181(0.087-0.378),P＜0.0001.4.Hainan Li TB patients and normal controls' allele gene analysis.The TGTG~- allele gene of Hainan Li ethnic were significantly higher than the control group,OR is 4.758(2.327-9.272).5.The factor of NRAMP1 gene polymorphisms and TB's Logistic analysis.OR of sex,cigarette,drink and TGTG-/TGTG- genotype frequencies and 3'UTR TGTG+/TGTGgenotype frequencies is 4.929(2.769-8.775),0.453(0.232-0.885),1.810(0.974-3.362);4.929 (2.769-8.775),5.140(2.394-11.034).Conclusion1 NRAMP1-D543N G/A genotype,NRAMPI-3'UTR TGTG-/TGTG~- genotype,NRAMPI-3'UTR TGTG~+/TGTG~- genotype and the frequency of allele gene are differences from country,nation and area.2 NRAMPI-3'UTR TGTG~-/TGTG~- genotype and NRAMPI-3'UTR TGTG~-/TGTG~- genotype are significantly higher in Hai nan Li ethnic TB patient than in control group,which is defferent from the study of tuberculosis in the Gambia,West Africa and hai nan in China. NRAMPI-3'UTR TGTG~-/TGTG~- genotype and NRAMPI-3'UTR TGTG~-/TGTG~- genotype might be involved in the susceptibility to TB among Hainan Li ethnic population.3 The factor of NRAMP1 gene polymorphisms and TB's Logistic analysis show that sex, cigarette,drink and TGTG~+/TGTG~-and TGTG~-/TGTG~- genotype might be involved in the susceptibility to TB among Hainan Li ethnic population.