Arji Naima, Busson Marc, Iraqi Ghali, Bourkadi Jamal Eddine, Benjouad Abdelaziz, Bouayad Abdellatif, Mariaselvam Christina, Salah Sofiane, Fortier Catherine, Amokrane Kahina, Marzais François, Boukouaci Wahid, Krishnamoorthy Rajagopal, Charron Dominique, El Aouad Rajae, Tamouza Ryad
National Institute of Hygiene, Agdal, Rabat, Morocco.
J Infect Dev Ctries. 2014 Apr 15;8(4):430-40. doi: 10.3855/jidc.3820.
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.
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.
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.
TLR2 and TLR4 interaction and a specific VDR haplotype influence protection against PTB in Moroccans patients.
Toll样受体（TLR）2、4以及维生素D受体（VDR）是抗结核分枝杆菌（Mtb）固有免疫和适应性免疫的核心组成部分。TLR2、TLR4和VDR基因多态性先前已与结核病（TB）相关，本文将其作为摩洛哥人群中肺结核（PTB）易感性的候选因素进行研究。
采用基于聚合酶链反应的限制性片段长度多态性和TaqMan单核苷酸多态性基因分型检测方法，对343例PTB患者和203例健康对照的基因组DNA进行分析，检测位于TLR2、TLR4和VDR基因中的12个单核苷酸多态性（SNP）。
TLR2 +597 CT基因型与预防PTB相关（校正p值[pc]=0.04；优势比[OR]=0.65；95%置信区间[CI]=0.45 - 0.94），TLR4 +7263 C等位基因与PTB易感性显著相关（pc = 0.04；OR = 1.63；CI = 1.06 - 2.57）。发现VDR [f,b,a,T]单倍型具有保护作用（pc < 0.00001；OR = 0.18；CI = 0.09 - 0.35），而TLR2 [-16934T,+597C,+1349T]单倍型似乎有风险（p = 0.03；OR = 1.52；CI = 1.01 - 2.30），但未达到统计学显著性。最后，对三个研究基因的多态性进行交叉分析发现，TLR2 +597和TLR4 +4434 SNP之间在预防PTB方面存在显著相互作用（pc = 0.036），表明功能相关的TLR4 +4434 SNP可能与TLR2 SNP协同作用。
TLR2和TLR4的相互作用以及特定的VDR单倍型影响摩洛哥患者对PTB的抵抗力。
