TY - JOUR
T1 - Genetic diversity of TLR2, TLR4, and VDR loci and pulmonary tuberculosis in moroccan patients
AU - Arji, Naima
AU - Busson, Marc
AU - Iraqi, Ghali
AU - Bourkadi, Jamal Eddine
AU - Benjouad, Abdelaziz
AU - Bouayad, Abdellatif
AU - Mariaselvam, Christina
AU - Salah, Sofiane
AU - Fortier, Catherine
AU - Amokrane, Kahina
AU - Marzais, François
AU - Boukouaci, Wahid
AU - Krishnamoorthy, Rajagopal
AU - Charron, Dominique
AU - El Aouad, Rajae
AU - Tamouza, Ryad
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Introduction: Toll-like receptors (TLRs) 2, 4, and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis (Mtb). TLR2, TLR4, and VDR polymorphisms were previously associated with tuberculosis (TB) and were here investigated as candidates for pulmonary TB (PTB) susceptibility in a Moroccan population group. Methodology: Genomic DNA from 343 PTB patients and 203 healthy controls were analyzed for 12 single nucleotide polymorphisms (SNPs) located in TLR2, TLR4, and VDR genes using polymerase chain reaction-based restriction fragment length polymorphism and TaqMan SNP genotyping assays. Results: The TLR2 +597 CT genotype was associated with protection against PTB (corrected p [pc] = 0.04; odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.45 - 0.94), and the TLR4 +7263 C allele was significantly associated with PTB susceptibility (pc = 0.04; OR = 1.63; CI = 1.06 - 2.57). The VDR [f,b,a,T] haplotype was found to confer protection (pc < 0.00001; OR = 0.18; CI = 0.09 - 0.35), while the TLR2 [-16934T,+597C,+1349T] haplotype seemed to be at risk (p = 0.03; OR = 1.52; CI = 1.01 - 2.30), but statistical significance was not reached. Finally, cross-analysis between polymorphisms of the three studied genes revealed significant interaction between TLR2 +597 and TLR4 +4434 SNPs towards protection against PTB (pc = 0.036), suggesting that the functionally relevant TLR4 +4434 SNP may act synergistically with TLR2 SNPs. Conclusions: TLR2 and TLR4 interaction and a specific VDR haplotype influence protection against PTB in Moroccans patients.
AB - Introduction: Toll-like receptors (TLRs) 2, 4, and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis (Mtb). TLR2, TLR4, and VDR polymorphisms were previously associated with tuberculosis (TB) and were here investigated as candidates for pulmonary TB (PTB) susceptibility in a Moroccan population group. Methodology: Genomic DNA from 343 PTB patients and 203 healthy controls were analyzed for 12 single nucleotide polymorphisms (SNPs) located in TLR2, TLR4, and VDR genes using polymerase chain reaction-based restriction fragment length polymorphism and TaqMan SNP genotyping assays. Results: The TLR2 +597 CT genotype was associated with protection against PTB (corrected p [pc] = 0.04; odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.45 - 0.94), and the TLR4 +7263 C allele was significantly associated with PTB susceptibility (pc = 0.04; OR = 1.63; CI = 1.06 - 2.57). The VDR [f,b,a,T] haplotype was found to confer protection (pc < 0.00001; OR = 0.18; CI = 0.09 - 0.35), while the TLR2 [-16934T,+597C,+1349T] haplotype seemed to be at risk (p = 0.03; OR = 1.52; CI = 1.01 - 2.30), but statistical significance was not reached. Finally, cross-analysis between polymorphisms of the three studied genes revealed significant interaction between TLR2 +597 and TLR4 +4434 SNPs towards protection against PTB (pc = 0.036), suggesting that the functionally relevant TLR4 +4434 SNP may act synergistically with TLR2 SNPs. Conclusions: TLR2 and TLR4 interaction and a specific VDR haplotype influence protection against PTB in Moroccans patients.
KW - Morocco
KW - Polymorphism
KW - Toll-like receptors
KW - Tuberculosis
KW - Vitamin D receptor
UR - http://www.scopus.com/inward/record.url?scp=84898401767&partnerID=8YFLogxK
U2 - 10.3855/jidc.3820
DO - 10.3855/jidc.3820
M3 - Article
C2 - 24727508
AN - SCOPUS:84898401767
SN - 2036-6590
VL - 8
SP - 430
EP - 440
JO - Journal of Infection in Developing Countries
JF - Journal of Infection in Developing Countries
IS - 4
ER -