A Study On The Association Of The Polymorphisms Of 3'UTR Of NRAMP1 Gene With Susceptibility To Tuberculosis In Hans

It was estimated that one-tenth of the world population who is infected with Mycobacterium tuberculosis will develop to clinical tuberculosis during their lifetime. From the beginning of last century, the relationship between genetic factor and susceptibility to tuberculosis has been studying consistently among inbred strains of mice, natural resistance to infection with several intracellular pathogens is controlled by a single dominant gene, designated Bcg(also known as Lsh/Ity). A candidate gene was isolated by positional cloning and designated the natural resistence associated macrophage protein 1 gene (Nrampl). A single nonconservative amino acid substitution of aspartic acid for glycine at position 169 is correlated with the susceptibility phenotype. That Nrampl and Beg are identical has been proved by the production of an Nrampl knockout mouse that is phenotypically identical to homozygous Nramp0169 mouse and by the restoration of the resistance phenotype in transgenic mice in which the Nramp I0169 allele are transferred onto the background of the NrampD169. It has been proved the human homologue of the Nrampl gene, designated NRAMP 1, is involved in susceptibility to Mycobacterium. Some polymorphisms, including 3'UTR(untranslated region), might influence the function of the gene. To determine whether polymorphisms in the 3'UTR of the NRAMP 1 gene are associated to tuberculosis in Hans, the polymorphism of 3'UTR of NRAMP 1 gene is typed by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphisms) among active tuberculosis patients and healthy individuals. We studied the relationship between polymorphisms in the 3'UTR and susceptibility to tuberculosis by statistics, after grouped cases according to genotype. In the tuberculosis patients, genotype TGTG/TGTG, TGTG/del, and del/del were observed in 95, 50 and 2 samples, respectively. However, the genotypes of the healthy controls were TGTG/TGTG in 115, TGTG/del in 29 and del/del in 1 sample. The proportioNRAMP1 3t@ 3-UTRof the genotype TGTG/TGTG were found more often among controls than patients ( x 2=7.79; P<0.01), as suggested that polymorphisms in the 3'UTR of NRAMP1 gene are associated with susceptibility to tuberculosis in Hans. The frequency of allele TGTG is 0.85 and the frequency of variant allele is 0.15. The same as that in Gambians and Koreans, the variant allele in Hans is more common than in Caucasians. These observations might explain in part why Hans have greater susceptibility to tuberculosis than Caucasians. It is interesting that the different proportions of variant allele in Gambians, Koreans and Hans in the cases and controls seem to indicate that the 3'UTR variants might not be the direct cause of susceptibility, but rather are strongly linked to an functional polymorphism.