VDR and TNF-alpha gene polymorphisms in Iranian tuberculosis patients: the study on host susceptibility

ABSTRACT

Vitamin-D receptor [VDR] and tumor necrosis factor-alpha [TNF-alpha] genes are thought to be important in the intracellular killing of mycobacteria. This study aimed to determine the association of VDR and TNF-alpha variant with development of pulmonary tuberculosis [PTB] among Iranian patients. Selected regions of VDR and TNF-alpha were amplified, and then the PCR products were digested using restriction enzyme [RFLP]. Digested products were run on 8% polyacrylamide gel, and were stained with silver-nitrate. Single nucleotide polymorphisms [SNPs] at restriction sites of BsmI, and FokI of VDR gene and SNPs of TNF-alpha at-238,-308,-244,-857,-863 positions were analyzed by PCR-RFLP among 117 PTB cases and 60 healthy controls. No statistically significant difference was observed in allele frequencies of FokI of VDR and TNF-alpha at-238,-244,-863 and-857 position. Although, the frequency of b allele of BsmI [p=0.001] and-308 A variant in TNF-alpha promoter region [p=0.006] were significantly more in PTB patients than healthy controls. The frequency of extended diplotypes were different in patients and control subjects [p<0.05]. This study confirmed the association of VDR BsmI and TNF-alpha-308A with susceptibility to tuberculosis in Iranian PTB patients. In addition, the results showed the importance of haplotypes and diplotypes analysis in determining the host susceptibility against TB