Stromal cell-derived factor-1 (SDF-1/CXCL12) gene polymorphisms in pulmonary tuberculosis patients of south India

CXCL12 gene polymorphisms influence CXCL12 levels and may be associated with the outcome of host-pathogen interaction. Hence, the present study was carried out to find out whether CXCL12 gene polymorphisms are associated with susceptibility or resistance to pulmonary tuberculosis (PTB). Intron and 3' untranslated region (UTR) polymorphisms of CXCL12 gene were investigated among 184 patients with PTB and 187 healthy controls (HC) using polymerase chain reaction-based methods. The results revealed an increased frequency of G/A genotype of In2 +5887 [P = 0.034; odds ratio (OR) 1.66; 95% confidence intervals 1.04-2.66] and a decreased frequency of G/A genotype of 3'UTR +12197 polymorphisms (P = 0.051; OR 0.64; 95% CI 0.4-1.00) among patients than HCs. When the study subjects were categorized based on sex, significantly increased frequencies of G/A genotype (P = 0.013 P(c) = 0.039; OR 2.41) of In2 +5887 and G/G genotype (P = 0.005, P(c) = 0.015; OR 2.48) of 3'UTR +12197 polymorphisms were observed among female patients with PTB as compared to female HC. A significantly decreased frequency of the haplotype G-C-A-T (P = 0.006, P(c) = 0.030; OR 0.48) was noticed among female patients with PTB as compared to female HC. The study suggests that G/A genotype of In2 +5887 and G/G genotype of 3'UTR +12197 polymorphisms may be associated with susceptibility to PTB among females, and the haplotype G-C-A-T of CXCL12 gene may be associated with protection in females.     

5′ Regulatory and 3′ Untranslated Region Polymorphisms of Vitamin D Receptor Gene in South Indian HIV and HIV–TB Patients

Introduction  Vitamin D receptor (VDR) gene polymorphisms in the 5′ regulatory region (Cdx2 and A-1012G), coding region (FokI), and 3′ untranslated region (UTR; BsmI, ApaI, and TaqI) were studied to find out whether these polymorphisms are associated with susceptibility to or protection against HIV-1 and development of tuberculosis (TB) in human immunodeficiency virus (HIV)-1-infected patients. Study Subjects and Methods  The study was carried out in 131 HIV patients without TB (HIV+ TB−) and 113 HIV patients with TB (HIV+ TB+; includes 82 patients with pulmonary TB (HIV+ PTB+) and 31 with extra pulmonary TB), 108 HIV-negative pulmonary TB patients (HIV− PTB+), and 146 healthy controls. Results  Among the 5′ regulatory and coding region polymorphisms, significantly increased frequency of G/A genotype of Cdx-2 was observed in HIV+ TB− group compared to controls (p = 0.012, odds ratio (OR) 1.89 95% confidence interval (CI) 1.14–3.15). In the 3′ UTR genotypes, a decreased frequency of b/b genotype of BsmI in total HIV patients (p = 0.014, OR 0.54 95% CI 0.32–0.89) and increased frequencies of A/A genotype of ApaI in HIV+ TB+ patients (p = 0.041, OR 1.77 95% CI 1.02–3.06) and t/t genotype of TaqI in HIV+ PTB+ patients (p = 0.05, OR 2.32 95% CI 0.99–5.46) were observed compared to controls. Haplotype analysis revealed significantly increased frequencies of 3′ UTR haplotype B-A-t in HIV+ TB+ and HIV+ PTB+ groups (Pc = 0.030, OR 1.75 95% CI 1.14–2.66) and decreased frequencies of b-A-T haplotype in total HIV patients (Pc = 0.012, OR 0.46 95% CI 0.27–0.77), HIV+ TB− (p = 0.031 OR 0.48 95% CI 0.25–0.89), and HIV+ PTB+ groups (Pc = 0.04, OR 0.47 95% CI 0.23–0.89) compared to controls. Conclusions  The results suggest that VDR gene 3′ UTR haplotype b-A-T may be associated with protection against HIV infection while B-A-t haplotype might be associated with susceptibility to development of TB in HIV-1-infected patients.     

Altered expressions of peripheral CD11c,CD80, CD83 markers and associations of HLA class II allele and haplotypes in self-limiting Hepatitis E infection

Hepatitis E virus (HEV), the major cause of self limiting viral hepatitis, is associated with a robust humoral, moderate CD4 T cell and CTL response. However, key questions like the probable involvement of HLA class II alleles and peripheral DCs/monocytes in regulating the innate and adaptive immune responses in Hepatitis E remain unanswered. One eighty four self- limiting Hepatitis E patients and 283 anti-HEV negative controls from Western India were studied for the distribution of HLA class II alleles and the frequencies of peripheral CD80, CD83, CD86, HLA-DR and CD11c by PCR SSP method and flow cytometry respectively. Frequency of DRB1^∗11 allele group was significantly low while haplotypes DRB1^∗15/DQB1^∗06 and DRB1^∗10/DQB1^∗05 were significantly high in the patient population. CD11c, CD80 and CD83 expressions were high in the patient groups. CD11c expression was positively associated with viral load. CD86 expression was significantly low in the patients having DQB1^∗06 allele. Association of HLA-DRB1^∗11 and the emergence of DRB1^∗15/DQB1^∗06 and DRB1^∗10/DQB1^∗05 as susceptible haplotypes towards HEV infection is being reported for the first time. Positive correlation of CD11c with HEV viral load suggested that increased frequencies of the same might be associated with HEV replication.