Department of Gastroenterology and Research Center of Digestive Diseases, Zhongnan Hospital, Wuhan University School of Medicine, Wuhan, People's Republic of China.
Int J Colorectal Dis. 2010 Feb;25(2):153-9. doi: 10.1007/s00384-009-0787-y. Epub 2009 Aug 7.
The highly polymorphic nonclassical MHC class I chain-related genes A and B (MICA and MICB) encode stress-inducible glycoproteins expressed on various epithelial cells including intestinal epithelial cells. MICA and MICB gene polymorphisms and expressions are associated with autoimmune diseases but not known in ulcerative colitis (UC).
To investigate the association of MICB exon 2-4 polymorphisms and soluble MICA (sMICA) expression with the susceptibility of UC in central China.
Genomic DNA was isolated from peripheral blood. The allele frequencies of MICB exon 2-4 were genotyped in 105 UC patients and 213 healthy controls by PCR single-stranded conformation polymorphism method. Thirty-two patients and 32 controls were selected for determining serum sMICA expression by ELISA.
Allele frequency of MICB0106 was significantly higher in UC patients than in healthy controls (19.0% vs. 8.9%, corrected P (Pc) = 0.0006), especially in patients with extensive colitis (24.4% vs. 8.9%, Pc = 0.0006), moderate and severe disease (24.1% vs. 8.9%, Pc = 0.0006), extraintestinal manifestations (20.5% vs. 8.9%, Pc = 0.012), male patients (22.1% vs. 8.0%, Pc = 0.006), and patients over the age of 40 years (28.8% vs. 8.3%, Pc = 0.0006). The sMICA level was significantly higher in UC than in healthy controls (604.41 +/- 480.43 pg/ml vs. 175.37 +/- 28.31 pg/ml, P = 0.0001) but not associated with the MICB0106 genotypes.
Overall, MICB0106 allele was positively associated with UC in the Han Chinese in central China. sMICA was highly expressed in UC but not associated with the MICB0106 genotype.
高度多态性的非经典 MHC Ⅰ类链相关基因 A 和 B(MICA 和 MICB)编码应激诱导的糖蛋白,表达于各种上皮细胞,包括肠道上皮细胞。MICA 和 MICB 基因多态性和表达与自身免疫性疾病有关,但在溃疡性结肠炎(UC)中尚不清楚。
研究 MICB 外显子 2-4 多态性和可溶性 MICA(sMICA)表达与中国中部 UC 易感性的关系。
从外周血中提取基因组 DNA。采用 PCR 单链构象多态性方法对 105 例 UC 患者和 213 例健康对照者的 MICB 外显子 2-4 等位基因频率进行基因分型。通过 ELISA 法测定 32 例患者和 32 例对照者血清 sMICA 的表达。
UC 患者 MICB0106 等位基因频率明显高于健康对照组(19.0%比 8.9%,校正 P(Pc)=0.0006),尤其是广泛结肠炎(24.4%比 8.9%,Pc=0.0006)、中重度疾病(24.1%比 8.9%,Pc=0.0006)、肠外表现(20.5%比 8.9%,Pc=0.012)、男性患者(22.1%比 8.0%,Pc=0.006)和年龄大于 40 岁的患者(28.8%比 8.3%,Pc=0.0006)。UC 患者 sMICA 水平明显高于健康对照组(604.41±480.43pg/ml 比 175.37±28.31pg/ml,P=0.0001),但与 MICB0106 基因型无关。
总体而言,中国中部汉族人群 MICB0106 等位基因与 UC 呈正相关。sMICA 在 UC 中高度表达,但与 MICB0106 基因型无关。