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, 29 (2), 196-204

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

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

K Alagarasu et al. J Clin Immunol.

Abstract

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.

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