dc.description.abstract | Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a leading public health problem worldwide and causes of death from infectious disease. Suppressors of cytokine signaling (SOCS) and gene single nucleotide polymorphisms (SNPs) play important roles in the protection against microbial infection and susceptibility to TB, respectively. However, no studies have demonstrated whether any of the eight SOCS family members are closely associated with TB in Taiwan and whether gene polymorphisms of SOCS-3, interferon gamma (IFNγ), SNP rs4331426, vitamin D receptor (VDR), and vitamin D binding protein (VDBP) are associated with the risk of TB. The overall objective of this dissertation was designed to examine the expression profiles of the eight SOCS families, as well as SNPs of SOCS-3, IFNγ, rs4331426, VDR, and VDBP, in association with tuberculosis. Chapter One discovered that SOCS gene expresses differently between active TB and healthy subjects with gender and age dependencies and that particular SOCS families, especially SOCS-3, allow discrimination of active TB from healthy and LTBI subjects. Chapter Two discovered that significant difference in genotype frequency for SOCS-3 SNP rs8064821 occurred between TB and non-TB groups of women but not men, and such findings may help explain the difference of SOCS-3 mRNA levels between male and female TB subjects. Chapter Three discovered that IFN-γ gene polymorphisms, particularly rs1861494, rs2069718, and rs2430561, were associated with susceptibility to tuberculosis in a Han Taiwanese population. Chapter Four discovered that VDR and VDBP SNPs were associated with susceptibility to tuberculosis in a Han Taiwanese population. Chapter Five discovered that SNP rs4331426 was associated with female but not with male TB in the Han Taiwanese population. Results of these studies lead us to be better understanding of the association between genetic risk factors and susceptibility to TB disease in Taiwan patients, as well as finding a biomarker for distinguishing active TB from LTBI and healthy subjects. | en_US |