Ding Yijuan, Xia Bing, Lü Min, Zhang Yan, Li Jin, Ye Mei, Luo Hesheng, Yu Jieping, Zhang Xiaolian, Tan Jingquan
Department of Gastroenterology, Renmin Hospital, Wuhan, Peoples Republic of China.
Clin Exp Immunol. 2005 Oct;142(1):193-8. doi: 10.1111/j.1365-2249.2005.02907.x.
The human MHC class I chain-related gene A (MICA) plays a role in regulating protective responses by intestinal epithelial Vdelta1 gamma delta T cells and the polymorphism of MICA were reported to be related to several autoimmune diseases. The present study aimed to investigate the association of the microsatellite polymorphisms of TM region of MICA gene with the susceptibility to ulcerative colitis (UC) in Chinese population. The microsatellite polymorphisms of the MICA were genotyped in unrelated 86 Chinese patients with UC and 172 ethnically matched healthy controls by a semiautomatic fluorenscently labelled PCR method. All the subjects were the Chinese with Han nationality. The frequency of MICA-A5.1 homozygous genotype and A5.1 allele were significantly increased in UC patients compared with healthy controls (22.1%versus 7%, P = 0.0009, Pc = 0.0126, OR = 3.781, 95%CI: 1.738-8.225 and 30.2%versus 17.4%, P = 0.0014, Pc = 0.007, OR = 2.051, 95%CI: 1.336-3.148, respectively). Adjusted the effects of gender and age at onset, MICA-A5.1 homozygous genotype and A5.1 allele were also increased in the UC patients. Moreover MICA-A5.1 allele was significantly increased in frequency in the female UC patients (38.2%versus 21.0%, P = 0.0095, Pc = 0.0475, OR = 2.326, 95%CI: 1.234-4.382). Logistic regression analysis also revealed that gender was independently associated with UC patients carried MICA-A5.1 allele (P = 0.046, OR (male) = 0.511, 95% CI: 0.264-0.987). Although the UC patients with extensive colitis (32.5%versus 17.4% in the healthy controls, P = 0.005, Pc = 0.025) and the UC patients with extraintestinal manifestations (36%versus 17.4% in the healthy controls, P = 0.0039, Pc = 0.0195) were more likely to carry the MICA-A5.1 allele, EIMs was associated with extent of disease (P < 0.0001, OR (with EIMs) = 3.511, 95% CI 1.747-7.056) and MICA-A5.1 allele was not associated with UC patients with extensive colitis or with EIMs in the logistic regression analysis. Therefore, the MICA-A5.1 homozygous genotype and A5.1 allele were closely associated with UC and the MICA-A5.1 allele was positively associated with the female UC patients in Chinese population.
人类主要组织相容性复合体(MHC)I类链相关基因A(MICA)在调节肠道上皮Vδ1γδT细胞的保护性反应中发挥作用,且据报道MICA的多态性与多种自身免疫性疾病相关。本研究旨在探讨中国人群中MICA基因跨膜(TM)区域微卫星多态性与溃疡性结肠炎(UC)易感性的关联。采用半自动荧光标记PCR方法,对86例无血缘关系的中国UC患者及172例种族匹配的健康对照进行MICA微卫星多态性基因分型。所有受试者均为汉族中国人。与健康对照相比,UC患者中MICA - A5.1纯合基因型和A5.1等位基因的频率显著增加(分别为22.1%对7%,P = 0.0009,Pc = 0.0126,OR = 3.781,95%CI:1.738 - 8.225;以及30.2%对17.4%,P = 0.0014,Pc = 0.007,OR = 2.051,95%CI:1.336 - 3.148)。校正发病时性别和年龄的影响后,UC患者中MICA - A5.1纯合基因型和A5.1等位基因的频率仍升高。此外,女性UC患者中MICA - A5.1等位基因频率显著增加(38.2%对21.0%,P = 0.0095,Pc = 0.0475,OR = 2.326,95%CI:1.234 - 4.382)。逻辑回归分析还显示,性别与携带MICA - A5.1等位基因的UC患者独立相关(P = 0.046,OR(男性)= 0.511,95%CI:0.264 - 0.987)。尽管广泛性结肠炎的UC患者(32.5%对健康对照中的17.4%,P = 0.005,Pc = 0.025)和有肠外表现的UC患者(36%对健康对照中的17.4%,P = 0.0039,Pc = 0.0195)更可能携带MICA - A5.1等位基因,但肠外表现与疾病范围相关(P < 0.0001,OR(有肠外表现)= 3.511, 95%CI 1.747 - 7.056),且在逻辑回归分析中,MICA - A5.1等位基因与广泛性结肠炎或有肠外表现的UC患者无关。因此,在中国人群中,MICA - A5.1纯合基因型和A5.1等位基因与UC密切相关,且MICA - A5.1等位基因与女性UC患者呈正相关。