Institute of Animal Genetics and Breeding, Sichuan Agricultural University, Chengdu Campus, Chengdu 611130, Sichuan, PR China.
J Anim Sci. 2013 Sep;91(9):4051-9. doi: 10.2527/jas.2013-6461. Epub 2013 Jul 26.
Dectin-1 plays a critical role in the pathogenesis of intestinal inflammation by recognizing the pathogenic agents and mediating cytokine responses. The objective of this study was to establish the association between dectin-1 polymorphisms and susceptibility to nonspecific digestive disorders (NSDD) and cytokine expression in rabbits. A total of 7 coding SNP were detected in dectin-1 gene. The genetic association between SNP (ss707197675A > G) and susceptibility to NSDD was evaluated using a case-control study (178 cases and 174 controls). The results revealed that the A allele was associated with an increased risk of developing NSDD in rabbits. The AA genotype significantly increased the genetic susceptibility to NSDD with odds ratio of 4.76 (95% confidence interval, 1.92-12.50, P = 0.0002) compared with GG and GA genotypes. We also experimentally induced NSDD in another independent growing rabbit population by feeding a low-fiber diet and subsequently investigated the cytokine mRNA expression. Among the 4 studied cytokines, the expression of interferon-γ, IL-17F, and IL-22 were increased 2.8 to 6.0-fold in AA genotype compared with GG genotype (P < 0.01). The greater IL-17F and IL-22 mRNA expressions indicated a positive correlation with severe intestinal inflammation (P < 0.05). The decreased expression of IL-10 was associated with severe intestinal inflammation (P = 0.006), but IL-10 expression was not influenced by dectin-1 genotype. In conclusion, polymorphism ss707197675 of dectin-1 is related with susceptibility to NSDD and increased expression of proinflammatory cytokines, and dectin-1 could be an important candidate gene associated with NSDD in rabbits.
Dectin-1 通过识别病原体并介导细胞因子反应,在肠道炎症发病机制中发挥关键作用。本研究旨在确定 dectin-1 多态性与非特异性消化障碍(NSDD)易感性和兔细胞因子表达之间的关联。在 dectin-1 基因中检测到 7 个编码 SNP。使用病例对照研究(178 例病例和 174 例对照)评估 SNP(ss707197675A > G)与 NSDD 易感性的遗传关联。结果表明,A 等位基因与兔 NSDD 的发病风险增加相关。与 GG 和 GA 基因型相比,AA 基因型显著增加了 NSDD 的遗传易感性,优势比为 4.76(95%置信区间,1.92-12.50,P = 0.0002)。我们还通过喂食低纤维饮食在另一个独立的生长兔群体中实验性诱导 NSDD,随后研究了细胞因子 mRNA 表达。在研究的 4 种细胞因子中,与 GG 基因型相比,AA 基因型的干扰素-γ、IL-17F 和 IL-22 表达增加了 2.8 至 6.0 倍(P < 0.01)。IL-17F 和 IL-22 mRNA 表达的增加与严重的肠道炎症呈正相关(P < 0.05)。IL-10 表达的减少与严重的肠道炎症相关(P = 0.006),但 IL-10 表达不受 dectin-1 基因型的影响。总之,dectin-1 的多态性 ss707197675 与 NSDD 的易感性和促炎细胞因子的表达增加有关,dectin-1 可能是与兔 NSDD 相关的重要候选基因。