de la Concha E G, Fernandez-Arquero M, Lopez-Nava G, Martin E, Allcock R J, Conejero L, Paredes J G, Diaz-Rubio M
Department of Immunology, Hospital Clinico San Carlos, Madrid, Spain.
Gastroenterology. 2000 Dec;119(6):1491-5. doi: 10.1053/gast.2000.20258.
BACKGROUND & AIMS: IKBL gene lies telomeric of the tumor necrosis factor cluster in the central major histocompatibility complex and carries a structural polymorphism at position +738. In the Spanish white population, we found the IKBL+738(C) allele in haplotypes carrying either HLA-DRB1()1501 or -DRB1()0103. Because these HLA class II alleles may confer susceptibility to ulcerative colitis, we investigated an association between IKBL+738(C) and this disease.
DNA-based techniques were used to type individual alleles of HLA-DRB1 and IKBL+738. The frequencies of these alleles were compared among ethnically matched populations comprising 155 patients and 298 controls.
IKBL+738(C) allele was exclusively increased in patients with extensive and/or intractable disease. HLA-DRB1()0103 was the only HLA-DRB1 allele to be significantly increased in frequency in patients with UC compared with controls. It was found in patients with extensive and distal disease. In the HLA-DRB1()0103-negative population, patients with extensive disease still had a significant association with IKBL+738(C). The difference between the 2 groups of patients was statistically significant (13.7% vs. 1.7% in patients with distal disease; odds ratio, 9.25; P = 0.01).
HLA-DRB1(*)0103 is associated with susceptibility to ulcerative colitis, and IKBL+738(C) marks a propensity to extensive and more severe disease.
IKBL基因位于主要组织相容性复合体中央肿瘤坏死因子簇的端粒区，在+738位点存在结构多态性。在西班牙白种人群中，我们发现IKBL +738（C）等位基因存在于携带HLA - DRB1（）1501或 - DRB1（）0103的单倍型中。由于这些HLA II类等位基因可能使个体易患溃疡性结肠炎，我们研究了IKBL +738（C）与该疾病之间的关联。
采用基于DNA的技术对HLA - DRB1和IKBL +738的个体等位基因进行分型。在由155例患者和298例对照组成的种族匹配人群中比较这些等位基因的频率。
IKBL +738（C）等位基因仅在广泛性和/或难治性疾病患者中增加。与对照组相比，HLA - DRB1（）0103是溃疡性结肠炎患者中频率显著增加的唯一HLA - DRB1等位基因。在广泛性和远端疾病患者中发现该等位基因。在HLA - DRB1（）0103阴性人群中，广泛性疾病患者与IKBL +738（C）仍有显著关联。两组患者之间的差异具有统计学意义（远端疾病患者中分别为13.7%和1.7%；优势比为9.25；P = 0.01）。
HLA - DRB1（*）0103与溃疡性结肠炎易感性相关，IKBL +738（C）标志着易患广泛性和更严重疾病的倾向。
