Genetic diversity of TLR2, TLR4, and VDR loci and pulmonary tuberculosis in Moroccan patients

  • Naima Arji National Institute of Hygiene, Agdal, Rabat, Morocco
  • Marc Busson AP-HP, IUH and INSERM, UMRS, 940, Saint-Louis Hospital, Paris, France
  • Ghali Iraqi Moulay Youssef Hospital, Ibn Sina University, Rabat, Morocco
  • Jamal Eddine Bourkadi Moulay Youssef Hospital, Ibn Sina University, Rabat, Morocco
  • Abdelaziz Benjouad Faculty of Sciences, Mohamed V University, Rabat, Morocco
  • Abdellatif Bouayad Faculty of Medicine and Pharmacy, Mohammed V Souissi University, Ibn Sina Hospital Rabat, Morocco.
  • Christina Mariaselvam AP-HP, IUH and INSERM, UMRS, 940, Saint-Louis Hospital, Paris, France
  • Sofiane Salah LabEx Transplantex, AP-HP, IUH and INSERM U940, Saint-Louis Hospital, Paris
  • Catherine Fortier AP-HP, IUH and INSERM, UMRS, 940, Saint-Louis Hospital, Paris, France
  • Kahina Amokrane AP-HP, IUH and INSERM, UMRS, 940, Saint-Louis Hospital, Paris, France
  • François Marzais AP-HP, IUH and INSERM, UMRS, 940, Saint-Louis Hospital, Paris, France
  • Wahid Boukouaci LabEx Transplantex, AP-HP, IUH and INSERM U940, Saint-Louis Hospital, Paris
  • Rajagopal Krishnamoorthy AP-HP, IUH and INSERM, UMRS, 940, Saint-Louis Hospital, Paris, France
  • Dominique Charron AP-HP, IUH and INSERM, UMRS, 940, Saint-Louis Hospital, Paris, France
  • Rajae El Aouad National Institute of Hygiene, Agdal, Rabat, Morocco
  • Ryad Tamouza AP-HP, IUH and INSERM, UMRS, 940, Saint-Louis Hospital, Paris, France
Keywords: toll-like receptors, vitamin D receptor, polymorphism, tuberculosis, Morocco

Abstract

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.

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Author Biographies

Sofiane Salah, LabEx Transplantex, AP-HP, IUH and INSERM U940, Saint-Louis Hospital, Paris
PharmD, PhD
Ryad Tamouza, AP-HP, IUH and INSERM, UMRS, 940, Saint-Louis Hospital, Paris, France
Associate Professor in Immunology and Immunogenetics
Published
2014-04-15
How to Cite
1.
Arji N, Busson M, Iraqi G, Bourkadi JE, Benjouad A, Bouayad A, Mariaselvam C, Salah S, Fortier C, Amokrane K, Marzais F, Boukouaci W, Krishnamoorthy R, Charron D, El AouadR, Tamouza R (2014) Genetic diversity of TLR2, TLR4, and VDR loci and pulmonary tuberculosis in Moroccan patients. J Infect Dev Ctries 8:430-440. doi: 10.3855/jidc.3820
Section
Original Articles

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