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

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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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Acknowledgements

This work was financially supported by Indian Council of Medical Research, New Delhi under HIV–TB Task force program, Project No.: 2003-05490. We also acknowledge the Indian Council of Medical Research, New Delhi for providing senior research fellowship to Mr. K. Alagarasu. We thank Ms. J. Chitra for the technical help rendered by her. We are indebted to all the patients and healthy volunteers who participated in the study.

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Authors and Affiliations

  1. Department of Immunology, Tuberculosis Research Center, Indian Council of Medical Research, Mayor V. R. Ramanathan Road, Chetput, Chennai, 600 031, India

    K. Alagarasu, P. Selvaraj & P. R. Narayanan

  2. Department of Clinical Research, Tuberculosis Research Center, Indian Council of Medical Research, Mayor V. R. Ramanathan Road, Chetput, Chennai, 600 031, India

    S. Swaminathan & G. Narendran

Authors
  1. K. Alagarasu
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  2. P. Selvaraj
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  3. S. Swaminathan
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  4. G. Narendran
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  5. P. R. Narayanan
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Corresponding author

Correspondence to P. Selvaraj.

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Alagarasu, K., Selvaraj, P., Swaminathan, S. et al. 5′ Regulatory and 3′ Untranslated Region Polymorphisms of Vitamin D Receptor Gene in South Indian HIV and HIV–TB Patients. J Clin Immunol 29, 196–204 (2009). https://doi.org/10.1007/s10875-008-9234-z

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  • DOI: https://doi.org/10.1007/s10875-008-9234-z

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