Coding and non-coding polymorphisms in VDR gene and susceptibility to pulmonary tuberculosis in tribes, castes and Muslims of Central India

Prithvi R. Sharma, Shweta Singh, Mamta Jena, Gunja Mishra, Ravi Prakash, P. K. Das, R. N.K. Bamezai, P. K. Tiwari

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Abstract

Vitamin D receptor (VDR) plays an important role in activating immune response against various infectious agents. This study was aimed to investigate the association between VDR gene polymorphisms and different clinical forms of pulmonary tuberculosis (TB) in different population groups. Four common polymorphisms (TaqI, ApaI, BsmI and FokI) of VDR gene were studied in clinically diagnosed TB patients and healthy controls from Sahariya tribe (n=377), Bhil tribe (n=95), Chhattisgarh tribe (n=33), general population from North-Central (NC) (n=1021) and South-Eastern (SE) region (n=646) and Muslims (n=217). Genotyping was carried out using PCR-RFLP method and re-confirmed by direct sequencing. The haplotype analysis was performed on Haploview 4.1 and statistical analysis was done using SPSS 13.0 software. We found that bb genotype of BsmI polymorphism conferred significant risk to smear positive and multiple drug resistant (MDR) TB in tribes [OR (CI)=3.7 (1.5-9.2), p=0.002], SE population [OR (CI)=2.1 (1.4-3.3), p=0.0004] and Muslims [OR (CI)=6.7 (1.1-39), p=0.01]. The subjects with FF genotype of FokI polymorphism appeared less likely (p=0.004) to develop MDR TB in NC population, whereas, those with Ff [OR (CI)=2.5 (1.3-5.0), p=0.004] and ff [OR (CI)=3.4 (1.2-9.3), p=0.01] genotypes were at high risk of MDR and smear positive disease, respectively. Similarly, tt genotype of TaqI polymorphism was found associated with high risk of smear positive TB in NC [OR (CI)=3.6 (0.9-14.2), p=0.05] as well as in SE [OR (CI)=4.7 (1.8-12.3), p=0.00003] population. Interestingly, tt genotype appeared strongly associated [OR (CI)=8.9 (2.7-29), p=0.00001] with high bacillary load outcome. In conclusion, genetic polymorphisms in VDR gene, alone or in combination (haplotypes) are associated with different clinical outcomes in pulmonary TB.

Original languageEnglish (US)
Pages (from-to)1456-1461
Number of pages6
JournalInfection, Genetics and Evolution
Volume11
Issue number6
DOIs
StatePublished - Aug 1 2011

Fingerprint

Muslims
Islam
Calcitriol Receptors
tuberculosis
caste
vitamin
vitamin D
Pulmonary Tuberculosis
Population Groups
Social Class
India
polymorphism
lungs
Genotype
genetic polymorphism
genotype
receptors
gene
Multidrug-Resistant Tuberculosis
Genes

Keywords

  • Haplotypes
  • Sahariya
  • TLR2
  • Tuberculosis
  • VDR

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Coding and non-coding polymorphisms in VDR gene and susceptibility to pulmonary tuberculosis in tribes, castes and Muslims of Central India. / Sharma, Prithvi R.; Singh, Shweta; Jena, Mamta; Mishra, Gunja; Prakash, Ravi; Das, P. K.; Bamezai, R. N.K.; Tiwari, P. K.

In: Infection, Genetics and Evolution, Vol. 11, No. 6, 01.08.2011, p. 1456-1461.

Research output: Contribution to journalArticle

Sharma, Prithvi R. ; Singh, Shweta ; Jena, Mamta ; Mishra, Gunja ; Prakash, Ravi ; Das, P. K. ; Bamezai, R. N.K. ; Tiwari, P. K. / Coding and non-coding polymorphisms in VDR gene and susceptibility to pulmonary tuberculosis in tribes, castes and Muslims of Central India. In: Infection, Genetics and Evolution. 2011 ; Vol. 11, No. 6. pp. 1456-1461.
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AU - Singh, Shweta

AU - Jena, Mamta

AU - Mishra, Gunja

AU - Prakash, Ravi

AU - Das, P. K.

AU - Bamezai, R. N.K.

AU - Tiwari, P. K.

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N2 - Vitamin D receptor (VDR) plays an important role in activating immune response against various infectious agents. This study was aimed to investigate the association between VDR gene polymorphisms and different clinical forms of pulmonary tuberculosis (TB) in different population groups. Four common polymorphisms (TaqI, ApaI, BsmI and FokI) of VDR gene were studied in clinically diagnosed TB patients and healthy controls from Sahariya tribe (n=377), Bhil tribe (n=95), Chhattisgarh tribe (n=33), general population from North-Central (NC) (n=1021) and South-Eastern (SE) region (n=646) and Muslims (n=217). Genotyping was carried out using PCR-RFLP method and re-confirmed by direct sequencing. The haplotype analysis was performed on Haploview 4.1 and statistical analysis was done using SPSS 13.0 software. We found that bb genotype of BsmI polymorphism conferred significant risk to smear positive and multiple drug resistant (MDR) TB in tribes [OR (CI)=3.7 (1.5-9.2), p=0.002], SE population [OR (CI)=2.1 (1.4-3.3), p=0.0004] and Muslims [OR (CI)=6.7 (1.1-39), p=0.01]. The subjects with FF genotype of FokI polymorphism appeared less likely (p=0.004) to develop MDR TB in NC population, whereas, those with Ff [OR (CI)=2.5 (1.3-5.0), p=0.004] and ff [OR (CI)=3.4 (1.2-9.3), p=0.01] genotypes were at high risk of MDR and smear positive disease, respectively. Similarly, tt genotype of TaqI polymorphism was found associated with high risk of smear positive TB in NC [OR (CI)=3.6 (0.9-14.2), p=0.05] as well as in SE [OR (CI)=4.7 (1.8-12.3), p=0.00003] population. Interestingly, tt genotype appeared strongly associated [OR (CI)=8.9 (2.7-29), p=0.00001] with high bacillary load outcome. In conclusion, genetic polymorphisms in VDR gene, alone or in combination (haplotypes) are associated with different clinical outcomes in pulmonary TB.

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