Kyo K, Muto T, Nagawa H, Lathrop G M, Nakamura Y
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Japan.
J Hum Genet. 2001;46(1):5-20. doi: 10.1007/s100380170118.
Ulcerative colitis (UC) and Crohn's disease (CD), the major forms of inflammatory bowel diseases (IBDs). are multifactorial disorders of unknown etiology. We reported a possible association of rare variable number of tandem repeat (VNTR) alleles of the "MUC3" gene with a susceptibility to UC. However, an entire structure of "MUC3" is still unknown because the long stretches of tandem repeats in this "gene" make its cloning extraordinarily difficult. In this study, we report evidence that "MUC3" consists of two genes, MUC3A and MUC3B, both of which encode membrane-bound mucins with two epidermal growth factor-like motifs, and we describe the complete 3'-terminal structures of these two genes. We have also analyzed the single nucleotide polymorphisms (SNPs) in the exonic sequences of the 3' portions of these two genes to investigate whether sequence variations in these regions can cause person-to-person differences in the susceptibility to IBDs, and report here that non-synonymous SNPs of MUC3A, involving a tyrosine residue with a proposed role in cell signaling, may confer genetic predisposition to CD (P = 0.0132). Our findings suggest that variants of MUC3A may be involved in the occurrence of UC and CD in distinct manners.
溃疡性结肠炎（UC）和克罗恩病（CD）是炎症性肠病（IBD）的主要形式，是病因不明的多因素疾病。我们报道了“MUC3”基因罕见的串联重复可变数目（VNTR）等位基因与UC易感性之间可能存在关联。然而，“MUC3”的完整结构仍然未知，因为该“基因”中长串联重复序列使其克隆极为困难。在本研究中，我们报告证据表明“MUC3”由两个基因MUC3A和MUC3B组成，这两个基因均编码具有两个表皮生长因子样基序的膜结合粘蛋白，并且我们描述了这两个基因完整的3'末端结构。我们还分析了这两个基因3'部分外显子序列中的单核苷酸多态性（SNP），以研究这些区域的序列变异是否会导致个体对IBD易感性的差异，并在此报告MUC3A的非同义SNP，涉及一个在细胞信号传导中起作用的酪氨酸残基，可能赋予CD遗传易感性（P = 0.0132）。我们的研究结果表明，MUC3A的变体可能以不同方式参与UC和CD的发生。
