ABSTRACT
BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to the activation of macrophages and the deficiency of vitamin D seems to be involved in the risk of tuberculosis (TB). The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and vitamin D receptor binding protein (VDBP) may be influenced by polymorphisms in the VDR and VDBP genes. In this study, variation in the VDR and VDBP genes was investigated in a Taiwanese population with TB. METHODS: We typed four VDR polymorphisms of restriction endonuclease sites for ApaI, TaqI, BsmI, and FokI and three VDBP polymorphisms-Thr420Lys, Asp416Glu, and Cys299Cys-in 198 patients with TB and 170 healthy volunteers. RESULTS: VDR TaqI, VDR BsmI, and VDBP Asp416Glu were significantly associated with TB susceptibility. Odd ratios of risk genotypes of the above three polymorphisms were 2.16 (95% confidence interval 1.01, 4.65), 2.14 (95% confidence interval 1.06, 4.31), and 2.24 (95% confidence interval 1.04, 4.80), respectively. VDBP haplotype analysis showed Gc1f carriers associated to TB. CONCLUSION: The polymorphisms in the VDR and VDBP genes appeared to be responsible for host susceptibility to human TB in a Taiwanese population.
Subject(s)
Genetic Predisposition to Disease , Receptors, Calcitriol/genetics , Tuberculosis/genetics , Vitamin D-Binding Protein/genetics , Female , Gene Frequency , Genotype , Humans , Macrophage Activation/genetics , Macrophage Activation/immunology , Macrophages/immunology , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , TaiwanABSTRACT
A single nucleotide polymorphism (SNP) rs4331426 located in a gene-poor region on chromosome 18q11.2 has been associated with tuberculosis (TB) by genome-wide association studies in Ghana and Gambia. In this study, we analyzed the SNP rs4331426 for its association with the risk of TB in the Taiwanese population. The SNP rs4331426 was genotyped in a case-control design that included 377 Han Taiwanese (200 TB patients and 177 controls) and was associated with TB (marginally significant p = 0.078). An increasingly significant association was observed after adjusting for sex in the logistic regression analysis (p = 0.029). Furthermore, the G carrier (AG genotype) conferred the risk of TB in females (p = 0.011), but not in males. These findings indicate that the SNP rs4331426 associated with TB in the Han Taiwanese population, especially in females. Further investigations on its role and that of the genomic region surrounding it are warranted.
Subject(s)
Chromosomes, Human, Pair 18/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide/genetics , Tuberculosis, Pulmonary/genetics , Asian People/genetics , Case-Control Studies , Female , Gene Frequency/genetics , Genome-Wide Association Study , Genotype , Humans , Male , Taiwan , Tuberculosis, Pulmonary/microbiologyABSTRACT
BACKGROUND: Polymorphisms of the interferon gamma (IFN-γ) gene are associated with the risk of tuberculosis (TB) in different populations. However, the genetic susceptibility to TB in Han Chinese living in Taiwan is still unknown. The purpose of this study is to evaluate whether the polymorphisms of the IFN-γ gene are associated with TB in Han Taiwanese. METHODS: A total of 200 TB patients and 202 age-matched non-TB individuals were enrolled. Five tag single nucleotide polymorphisms (tSNPs) and rs2430561 (+874) of IFN-γ were selected from a public database. The genotypes were determined using polymerase chain reaction assays. RESULTS: Three IFN-γ polymorphisms in intron 3, rs1861494 and rs2069718, and rs2430561 in interon 1 were strongly associated with TB. The C carrier (CT+TT) of rs1861494, TT homozygous of rs2069718, and AA homozygous of rs2430561 were risk genotypes for susceptibility to TB. CONCLUSION: The IFN-γ polymorphisms, rs1861494, rs2069718, and rs2430561, may confer the risk of TB in Han Taiwanese.
Subject(s)
Genetic Predisposition to Disease , Interferon-gamma/genetics , Tuberculosis/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , Ethnicity , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Taiwan , Tuberculosis/immunologyABSTRACT
OBJECTIVES: The aim of this study was to delineate the association between high macrophage migration inhibitory factor (MIF) and interleukin 10 (IL-10) levels in the early phase of sepsis and rapidly fatal outcome. METHODS: One hundred and fifty-three adult subjects with the main diagnosis of severe sepsis (including septic shock) admitted directly from the emergency department of two tertiary medical centers and one regional teaching hospital between January 2009 and December 2011, were included prospectively. MIF and IL-10 levels were measured and outcomes were analyzed by Cox regression analysis according to the following outcomes: rapidly fatal outcome (RFO, death within 48 h), late fatal outcome (LFO, death between 48 h and 28 days), and survival at 28 days. RESULTS: Among the three outcome groups, IL-10 levels were significantly higher in the RFO group (p < 0.001) and no significant differences were seen between the LFO and survivor groups. After Cox regression analysis, each incremental elevation of 1000 pg/ml in both IL-10 and MIF was independently associated with RFO in patients with severe sepsis. Each incremental elevation of 1000 pg/ml in IL-10 increased the RFO risk by a factor of 1.312 (95% confidence interval 1.094-1.575; p=0.003); this was the most significant factor leading to RFO in patients with severe sepsis. CONCLUSIONS: Patients with RFO exhibited simultaneously high MIF and IL-10 levels in the early phase of severe sepsis. Incremental increases in both IL-10 and MIF levels were associated with RFO in this patient group, and of the two, IL-10 was the most significant factor linked to RFO.
