目的:精神分裂症(SZ)是一种多因素疾病,涉及遗传和环境因素之间的复杂相互作用,在那里,免疫功能障碍起着关键的致病作用。为了探索SZ固有免疫反应的控制,我们旨在研究12种TLR2,TLR4和TLR9变体之间的潜在关联(TLR2:rs4696480T>A,rs3804099T>C,rs3804100T>C;TLR4:rs1927914G>A,rs10759932T>C,rs4986790A>G,rs4986791T>C,rs11536889G>C,rs11536891T>C;TLR9:rs187084A>G,突尼斯人的rs352139T>C和rs352140C>T)和SZ易感性。
方法:本研究包括150名患者和201名没有精神病史的健康对照。使用TaqManSNP基因分型测定进行基因分型。我们还使用Haploview4.2软件评估了具有SZ的TLR2、TLR4和TLR9变体的单倍型分析。
结果:我们发现TLR2rs4696480T>A变体的AA基因型与SZ的风险增加显着相关(46%vs.31%,P=4.7×10-3,OR=1.87和95%CI[1.18-2.97])。对照组的TA基因型频率明显高于SZ患者(27%vs.43%,P=2.1×10-3),可能与对SZ的保护有关(OR=0.49和95%CI[0.30-0.80])。然而,与患者相比,对照组的TLR9rs187084-GG基因型更高(16%vs.5%,P=1.6×10-3),并对SZ具有保护作用(OR=0.28,CI=[0.10-0.68])。TLR2的ACT单倍型和TLR9基因的ACC单倍型被鉴定为SZ的风险单倍型(P=0.04,OR=9.30,95%CI=[1.11-77.71];P=3×10-4,OR=6.05,95%CI=[2.29-15.98],分别)。
结论:结果表明,TLR2和TLR9的遗传多样性可能在对SZ的遗传脆弱性中起作用。然而,包括更多的患者,建议评估TLR2和TLR9的表达。
OBJECTIVE: Schizophrenia (SZ) is a multifactorial disorder involving complex interactions between genetic and environmental factors, where immune dysfunction plays a key etiopathogenic role. In order to explore the control of innate immune responses in SZ, we aimed to investigate the potential association between twelve TLR2, TLR4 and TLR9 variants (TLR2: rs4696480T>A, rs3804099T>C, rs3804100T>C; TLR4: rs1927914G>A, rs10759932T>C, rs4986790A>G, rs4986791T>C, rs11536889G>C, rs11536891T>C; TLR9: rs187084A>G, rs352139T>C and rs352140C>T) and SZ susceptibility in a Tunisian population.
METHODS: This study included 150 patients and 201 healthy controls with no history of psychiatric illness. Genotyping was done using a TaqMan SNP genotyping assay. We also assessed a haplotype analysis for TLR2, TLR4 and TLR9 variants with SZ using Haploview 4.2 Software.
RESULTS: We found that the AA genotype of the TLR2 rs4696480T>A variant was significantly associated with an increased risk of SZ (46% vs. 31%, P=4.7×10-3, OR=1.87 and 95% CI [1.18-2.97]). The frequency of the TA genotype was significantly higher in the control group than in SZ patients (27% vs. 43%, P=2.1×10-3) and may be associated with protection against SZ (OR=0.49 and 95% CI [0.30-0.80]). Whereas, the TLR9 rs187084-GG genotype was higher in the control group compared to patients (16% vs. 5%, P=1.6×10-3) and would present protection against SZ (OR=0.28, CI=[0.10-0.68]). The ACT haplotype of the TLR2 and the ACC haplotype of the TLR9 gene were identified as a risk haplotypes for SZ (P=0.04, OR=9.30, 95% CI=[1.11-77.71]; P=3×10-4, OR=6.05, 95% CI=[2.29-15.98], respectively).
CONCLUSIONS: The results indicate that TLR2 and TLR9 genetic diversity may play a role in genetic vulnerability to SZ. However, including more patients and evaluation of TLR2 and TLR9 expression are recommended.