Wolters Victorien M, Verbeek Wieke H M, Zhernakova Alexandra, Onland-Moret Charlotte, Schreurs Marco W J, Monsuur Alienke J, Verduijn Willem, Wijmenga Cisca, Mulder Chris J J
Department of Pediatric Gastroenterology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Clin Gastroenterol Hepatol. 2007 Dec;5(12):1399-405, 1405.e1-2. doi: 10.1016/j.cgh.2007.08.018. Epub 2007 Oct 29.
BACKGROUND & AIMS: Celiac disease (CD) is associated with HLA-DQ2 and HLA-DQ8 and has been linked to genetic variants in the MYO9B gene on chromosome 19. HLA-DQ2 homozygosity is associated with complications of CD such as refractory celiac disease type II (RCD II) and enteropathy-associated T-cell lymphoma (EATL). We investigated whether MYO9B also predisposes to RCD II and EATL.
Genotyping of MYO9B and molecular HLA-DQ2 typing were performed on 62 RCD II and EATL patients, 421 uncomplicated CD patients, and 1624 controls.
One single nucleotide polymorphism in MYO9B showed a significantly different allele distribution in RCD II and EATL patients compared with controls (P = .00002). The rs7259292 T allele was significantly more frequent in RCD II and EATL patients compared with CD patients (P = .0003; odds ratio [OR], 3.61; 95% confidence interval [CI], 1.78-7.31). The frequency of the haplotype carrying the T allele of this single nucleotide polymorphism was significantly increased in RCD II and EATL patients (11%), compared with controls (2%) and CD patients (3%) (OR, 6.76; 95% CI, 3.40-13.46; P = 2.27E-09 and OR, 4.22; 95% CI, 1.95-9.11; P = .0001, respectively). Both MYO9B rs7259292 and HLA-DQ2 homozygosity increase the risk for RCD II and EATL to a similar extent when compared with uncomplicated CD patients (OR, 4.3; 95% CI, 1.9-9.8 and OR, 5.4; 95% CI, 3.0-9.6, respectively), but there was no evidence for any interaction between these 2 risk factors.
We show that both MYO9B and HLA-DQ2 homozygosity might be involved in the prognosis of CD and the chance of developing RCD II and EATL.
乳糜泻（CD）与HLA - DQ2和HLA - DQ8相关，并且与19号染色体上MYO9B基因的遗传变异有关。HLA - DQ2纯合性与CD的并发症如II型难治性乳糜泻（RCD II）和肠病相关T细胞淋巴瘤（EATL）有关。我们研究了MYO9B是否也易导致RCD II和EATL。
对62例RCD II和EATL患者、421例无并发症的CD患者以及1624名对照者进行了MYO9B基因分型和HLA - DQ2分子分型。
与对照者相比，RCD II和EATL患者中MYO9B的一个单核苷酸多态性显示出明显不同的等位基因分布（P = 0.00002）。与CD患者相比，RCD II和EATL患者中rs7259292 T等位基因的频率显著更高（P = 0.0003；优势比[OR]，3.61；95%置信区间[CI]，1.78 - 7.31）。与对照者（2%）和CD患者（3%）相比，携带该单核苷酸多态性T等位基因的单倍型在RCD II和EATL患者中的频率显著增加（11%）（OR，6.76；95% CI，3.40 - 13.46；P = 2.27E - 09和OR，4.22；95% CI，1.95 - 9.11；P = 0.0001）。与无并发症的CD患者相比，MYO9B rs7259292和HLA - DQ2纯合性使RCD II和EATL的风险增加程度相似（OR分别为4.3；95% CI，1.9 - 9.8和OR，5.4；95% CI，3.0 - 9.6），但没有证据表明这两个风险因素之间存在任何相互作用。
我们表明，MYO9B和HLA - DQ2纯合性可能都与CD的预后以及发生RCD II和EATL的可能性有关。
Zotero 插件