Pathan S, Gowdy R E, Cooney R, Beckly J B, Hancock L, Guo C, Barrett J C, Morris A, Jewell D P
Department of Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Tissue Antigens. 2009 Oct;74(4):322-9. doi: 10.1111/j.1399-0039.2009.01314.x. Epub 2009 Jul 29.
Linkage in families and association in population case-control investigations have clearly shown that genes within the major histocompatibility complex region on chromosome 6p are relevant to the susceptibility and pathogenesis of ulcerative colitis (UC) and Crohn's disease. However, identifying the causative variants by fine mapping has not been conclusive. In this study using 58 single nucleotide polymorphisms (SNPs) with 616 UC cases, there was significant association with SNP rs2294881 of the (butyrophilin-like 2) BTNL2 gene with odds ratio (OR) = 2.80, confidence interval (CI) = 1.62-4.84 and P = 5.69 x 10(-4) (P(Bonferroni) = 3.3 x 10(-2)) and replication of SNP rs9268480. The missense SNP rs2076523 (K196E) showed novel association with a subset of UC cases with colectomy (n = 126), OR = 0.25, CI = 0.11-0.58 and P = 4.42 x 10(-4) (P(Bonferroni) = 2.56 x 10(-2)). These three associated variants within the BTNL2 gene were neither in linkage disequilibrium with each other nor correlated with the SNPs tagging the human leukocyte antigen (HLA)-DRB11502 and HLA-DRB10301 alleles.
家族连锁分析和人群病例对照研究中的关联分析均清楚表明，位于6号染色体短臂主要组织相容性复合体区域内的基因与溃疡性结肠炎（UC）和克罗恩病的易感性及发病机制相关。然而，通过精细定位来确定致病变异尚未得出定论。在本研究中，对616例UC病例使用了58个单核苷酸多态性（SNP），发现（嗜乳脂蛋白样2）BTNL2基因的SNP rs2294881存在显著关联，比值比（OR）=2.80，置信区间（CI）=1.62 - 4.84，P = 5.69×10⁻⁴（经Bonferroni校正的P = 3.3×10⁻²），并且SNP rs9268480得到了重复验证。错义SNP rs2076523（K196E）显示与接受结肠切除术的一部分UC病例（n = 126）存在新的关联，OR = 0.25，CI = 0.11 - 0.58，P = 4.42×10⁻⁴（经Bonferroni校正的P = 2.56×10⁻²）。BTNL2基因内的这三个相关变异彼此之间既不存在连锁不平衡，也与标记人类白细胞抗原（HLA）-DRB11502和HLA-DRB10301等位基因的SNP不相关。
