MHC class I chain-related gene A-A5•1 allele is associated with ulcerative colitis in Chinese population

MHC class I chain-related gene A-A5•1 allele is associated with ulcerative colitis in Chinese population
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DOI:
10.1111/j.1365-2249.2005.02907.x
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发表时间:
2005-10-01
影响因子:
4.6
通讯作者:
Tan, JQ
Tan, JQ
中科院分区:
医学3区
文献类型:
--
作者:
Ding, YJ;Xia, B;Tan, JQ

文献摘要

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人类MHC I类链相关基因A(MICA)在调节肠道上皮细胞V Delta 1γDelta T细胞的保护性反应中起着重要作用,其多态性与多种自身免疫性疾病有关。本研究旨在探讨MICA基因TM区微卫星多态性与中国人群溃疡性结肠炎(UC)易感性的关系。采用半自动荧光标记聚合酶链式反应技术,对86例无关中国人UC患者和172例健康对照的MICA基因进行了基因分型。所有受试者均为汉族中国人。UC患者MICA-A5.1纯合子和A5.1等位基因频率显著高于健康对照组(分别为22.1%和7%,P=0.0009,Pc=0.0126,OR=3.781,95%CI:1.738~8.225和30.2%比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,UC患者的MICA-A5.1纯合子基因和A5.1等位基因也增加。女性UC患者MICA-A5.1等位基因频率显著增加(38.2%vs21.0%,P=0.0095,Pc=0.0475,OR=2.326,95%CI:1.234~4.382)。Logistic回归分析还显示性别与UC患者携带MICA-A5.1等位基因有关(P=0.046,OR(男性)=0.511,95%CI:0.264~0.987)。尽管有广泛结肠炎的UC患者(32.5%比健康对照组的17.4%,P=0.005,Pc=0.025)和有肠外症状的UC患者(36%比17.4%,P=0.0039,Pc=0.0195)更有可能携带MICA-A5.1等位基因,但EIMS与疾病的程度有关(P<Logistic回归分析显示,MICA-A5.1等位基因和MICA-A5.1等位基因与UC合并广泛性结肠炎或EIMS无关。因此,MICA-A5.1纯合子和A5.1等位基因与UC密切相关,MICA-A5.1等位基因与女性UC呈正相关。
The human MHC class I chain-related gene A (MICA) plays a role in regulating protective responses by intestinal epithelial V delta 1 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.