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

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

Comparison of Nramp1 gene polymorphism among TB health care workers and recently infected cases; Assessment of host susceptibility

A link between polymorphisms in the natural resistance -associated macrophage protein gene 1 [Nramp] and susceptibility to tuberculosis [TB] has been demonstrated worldwide. This study aimed to investigate the Nramp1 gene variants among workers exposed to TB bacilli [1-2 hours per day for 1 to 20 years] who did not develop the diseases with those who developed the disease through recent transmission. The polymorphism of Nramp1 at INT4, D543 and 3'UTR was examined in 71 newly smear-positive TB cases and 39 healthcare workers exposed to TB. Polymerase chain reaction [PCR] and restriction fragment length polymorphism [RFLP] were used to genotype Nramp1 polymorphism. Patients' clinical and demographical data were collected. The heterozygote patterns of INT4 [G/C], D543 [G/A] and 3'UTR [+/del] occurred more frequently in control subjects than in patients [P =0.012], respectively [odds: 1.9 CI95%] [1.13-3.12]. Although, the homozygous patterns of INT4 [C/C; 8.5%], D543 [A/A; 1.4%] and 3'UTR [del/del; 1.4%] were only seen in patients [sensitivity 11% and specificity 100%]. The other risk factors like gender, age, resistance and PPD were not associated with Nramp1 gene polymorphism. Individuals with homozygous type mutation have an increased risk of developing tuberculosis. Therefore, we suggest detection of Nramp1 variants in high-risk groups i.e., health workers and close contact cases