Costa Pereira Cristiana, Durães Cecília, Coelho Rosa, Grácio Daniela, Silva Marco, Peixoto Armando, Lago Paula, Pereira Márcia, Catarino Telmo, Pinho Salomé, Teixeira João Paulo, Macedo Guilherme, Annese Vito, Magro Fernando
Department of Environmental Health, National Institute of Health Dr. Ricardo Jorge, Oporto, Portugal.
MedInUP - Centre for Drug Discovery and Innovative Medicines, University of Porto, Oporto, Portugal.
PLoS One. 2017 Jan 4;12(1):e0169102. doi: 10.1371/journal.pone.0169102. eCollection 2017.
Inflammation is the driving force in inflammatory bowel disease (IBD) and its link to oxidative stress and carcinogenesis has long been accepted. The antioxidant system of the intestinal mucosa in IBD is compromised resulting in increased oxidative injury. This defective antioxidant system may be the result of genetic variants in antioxidant genes, which can represent susceptibility factors for IBD, namely Crohn's disease (CD) and ulcerative colitis (UC). Single nucleotide polymorphisms (SNPs) in the antioxidant genes SOD2 (rs4880) and GPX1 (rs1050450) were genotyped in a Portuguese population comprising 436 Crohn's disease and 367 ulcerative colitis patients, and 434 healthy controls. We found that the AA genotype in GPX1 is associated with ulcerative colitis (OR = 1.93, adjusted P-value = 0.037). Moreover, we found nominal significant associations between SOD2 and Crohn's disease susceptibility and disease subphenotypes but these did not withstand the correction for multiple testing. These findings indicate a possible link between disease phenotypes and antioxidant genes. These results suggest a potential role for antioxidant genes in IBD pathogenesis and should be considered in future association studies.
炎症是炎症性肠病（IBD）的驱动力，其与氧化应激和致癌作用的联系早已得到认可。IBD患者肠黏膜的抗氧化系统受损，导致氧化损伤增加。这种有缺陷的抗氧化系统可能是抗氧化基因遗传变异的结果，这些变异可能是IBD（即克罗恩病（CD）和溃疡性结肠炎（UC））的易感因素。在一个由436例克罗恩病患者、367例溃疡性结肠炎患者和434例健康对照组成的葡萄牙人群中，对抗氧化基因SOD2（rs4880）和GPX1（rs1050450）的单核苷酸多态性（SNP）进行了基因分型。我们发现，GPX1基因的AA基因型与溃疡性结肠炎相关（比值比=1.93，校正P值=0.037）。此外，我们发现SOD2与克罗恩病易感性及疾病亚表型之间存在名义上的显著关联，但这些关联在多重检验校正后并不成立。这些发现表明疾病表型与抗氧化基因之间可能存在联系。这些结果提示抗氧化基因在IBD发病机制中可能起作用，应在未来的关联研究中予以考虑。
