Studies on the association between VDR gene polymorphisms and susceptibility to tuberculosis in the Romanian population

V. Stoian, N. Constantin, A. Simon-Gruita, F. Stanciu, G. Duta-Cornescu, D. Banica, R. Tuduce and P. Cristea. Poster at 6th European Cytogenetics Conference (6th ECC). 7-10 July, 2007. Istanbul-Turkey. Chromosome Research (2007). pp.258. Poster 13.1-P


Epidemiologic and laboratory studies suggest a correlation between vitamin D metabolism and immunity to TB; single nucleotide polymorphism (SNP) on vitamin D receptor (VDR) gene seems to influence in certain ethnic groups the host response to Mycobacterium tuberculosis. VDR gene located on chromosome 12 (12q12-14) has 15 exons span on approximately 75 kb. The goal of our study is to find out whether VDR gene variants are associated in the Romanian population with the susceptibility to TB. The case-control study carried out on TB patients and healthy control group tries to identify two VDR gene polymorphisms, defined by the restriction endonucleases ApaI and TaqI. For VDR genotyping, PCR-RFLP and ARMS-PCR methods were used. With the first method a 740 bp amplified DNA fragment is subjected to the restriction enzyme digestion. The second method uses sequence specific primers to amplify the four haplotypes generated by ApaI and TaqI polymorphisms. Thus, wild and mutant alleles (A, T and a, t respectively) and the corresponding genotypes (AA, Aa, aa and TT, Tt, tt) were identified. The results were statistically analyzed to determine the possible association between these polymorphisms and sensibility/resistance to TB in the Romanian population. Preliminary data show that the wild allele A frequency in TB patients (0,64) is greater than in control group (0,56), but allele T frequency is approximately equal in both groups (0,61 in patients and 0,60 in control). The genotype frequencies revealed the heterozygote predominance for ApaI polymorphism with a higher value registered in TB patients (0,64 and 0,52 respectively). For the TaqI polymorphisms the TT genotypes were better represented in TB patients (0,77) than in the control (0,43) but exceeded the frequencies of the other genotypes. For further development of the study a comparison regarding the correlation between these polymorphisms and TB susceptibility in different geographic zones of Romania will be done.