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Scand J Immunol. 2012 Jun;75(6):568-87. doi: 10.1111/j.1365-3083.2012.02696.x.

DNA sequence variation and regulation of genes involved in pathogenesis of pulmonary tuberculosis.

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1
Department of Biochemistry, Dr. R.M.L. Avadh University, Faizabad, U.P., India.

Abstract

DNA sequence variations [copy number variations, single nucleotide polymorphisms (SNPs) and microsatellite repeats] play an important role in susceptibility/resistance to tuberculosis and other infectious diseases like malaria and HIV. Different population exhibit variable associations with tuberculosis susceptibility and severity because of DNA sequence variations in both host and parasite. A number of genes and their polymorphisms have been identified that appear to be important in tuberculosis. In this article, several case-control studies of tuberculosis including a number of genes in different population have been explored. Furthermore, this review summarizes the current studies of host polymorphisms and their association with tuberculosis in different population. We have computationally predicted 275 SNPs which occur in transcription factor binding sites for transcription factors in 19 genes involved in pathogenesis of tuberculosis. Some common SNPs are rs1327474, rs755622, rs1801274, rs396991, rs5030737, rs1800451, rs1800450, rs3763313 rs3763313, rs9268494 and rs9268492 that have been found to play a role in disease. Presence of non-synonimous polymorphisms in coding region might affect the structure of protein, whereas polymorphisms in promoter region affect the level of gene products, consequently altering the susceptibility/resistance to disease. Based on this prediction, we hypothesize that these genes play an important role in susceptibility to tuberculosis through an altered expression of gene product via the modification of transcriptional regulation of gene.

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