Laboratory of Genetics, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece.
Gastroenterology Department, University General Hospital of Larissa, 41110 Larissa, Greece.
Genes (Basel). 2023 Feb 9;14(2):445. doi: 10.3390/genes14020445.
The clinical heterogeneity regarding the response profile of the antitumor necrosis factor (anti-TNF) in patients with Crohn's disease (CD) and psoriasis (PsO) is attributed, amongst others, to genetic factors that influence the regulatory mechanisms which orchestrate the inflammatory response. Here, we investigated the possible associations between the rs2910164 and rs767649 variants and the response to anti-TNF therapy in a Greek cohort of 103 CD and 100 PsO patients. We genotyped 103 CD patients and 100 PsO patients via the PCR-RFLP method, utilizing the de novo formation of a restriction site for the SacI enzyme considering the rs2910164, while Tsp45I was employed for the rs767649 variant. Additionally, we investigated the potential functional role of the rs767649 variant, exploring in silico the alteration of transcription factor binding sites (TFBSs) mapped on its genomic location. Our single-SNP analysis displayed a significant association between the rare rs767649 A allele and response to therapy (Bonferroni-corrected value = 0.012) in patients with PsO, a result further enhanced by the alteration in the IRF2 TFBS caused by the above allele. Our results highlight the protective role of the rare rs767649 A allele in the clinical remission of PsO, implying its utilization as a pharmacogenetic biomarker.
肿瘤坏死因子（anti-TNF）在克罗恩病（CD）和银屑病（PsO）患者中的抗肿瘤反应谱存在临床异质性，其原因之一是遗传因素影响调节炎症反应的调控机制。在这里，我们研究了希腊 103 名 CD 患者和 100 名 PsO 患者中 rs2910164 和 rs767649 变体与抗 TNF 治疗反应之间的可能关联。我们通过 PCR-RFLP 方法对 103 名 CD 患者和 100 名 PsO 患者进行基因分型，考虑到 rs2910164 新形成了一个 SacI 酶的酶切位点，而 Tsp45I 则用于 rs767649 变体。此外，我们还研究了 rs767649 变体的潜在功能作用，通过在其基因组位置上探索转录因子结合位点（TFBS）的改变来研究其功能。我们的单核苷酸多态性分析显示，在 PsO 患者中，罕见的 rs767649 A 等位基因与治疗反应之间存在显著关联（经 Bonferroni 校正的 值=0.012），该等位基因改变了 IRF2 TFBS，进一步增强了这一结果。我们的结果强调了罕见的 rs767649 A 等位基因在 PsO 临床缓解中的保护作用，暗示其可用作药物遗传学生物标志物。
