5' regulatory and 3' untranslated region polymorphisms of vitamin D receptor gene in south Indian HIV and HIV–TB patients.

Alagarasu, K.; Selvaraj, P.; Swaminathan, S.; Narendran, G.; Narayanan, P.R.

Journal of Clinical Immunology; 2009; 29; 196–204.

Abstract: Introduction: Vitamin D receptor (VDR) gene polymorphisms in the 5' regulatory region (Cdx2 and A-1012G), coding region ( Fok I), and 3' untranslated region (UTR; Bsm I, Apa I, and Taq I) 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 Bsm I in total HIV patients ( p =0.014, OR 0.54 95% CI 0.32– 0.89) and increased frequencies of A/A genotype of Apa I in HIV+ TB+ patients ( p =0.041, OR 1.77 95% CI 1.02–3.06) and t/t genotype of Taq I 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.

Keywords: Vitamin D receptor - polymorphisms - HIV-1 – tuberculosis - HIV–TB

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