Ulcerative colitis: a genetically heterogeneous disorder defined by genetic (HLA class II) and subclinical (antineutrophil cytoplasmic antibodies) markers.
Ulcerative colitis: a genetically heterogeneous disorder defined by genetic (HLA class II) and subclinical (antineutrophil cytoplasmic antibodies) markers.
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溃疡性结肠炎：一种由遗传（HLA II 类）和亚临床（抗中性粒细胞胞浆抗体）标记物定义的遗传异质性疾病。
DOI：
10.1172/jci116613
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Targan,SR
中科院分区：
文献类型：
--
作者：
Yang,H;Rotter,JI;Toyoda,H;Landers,C;Tyran,D;McElree,CK;Targan,SR
新近描述的HLA II类基因与溃疡性结肠炎（UC）（DR 2）和克罗恩病（CD）（DR 1/DQ 5）的不同关联为这两种形式的炎症性肠病之间的易感性的遗传异质性提供了强有力的证据。抗神经细胞胞浆抗体（ANCA，UC的亚临床标志物）在UC家族中的家族性分布进一步暗示了UC内异质性的存在。为了验证ANCA所指示的UC内的异质性具有位于HLA区域内的遗传基础的假设，我们研究了89例UC病例和种族匹配的对照组（n = 50）。应用血清学和分子分型技术确定HLA Ⅱ类基因（DR、DQ）。ANCA检测使用酶联免疫吸附试验，并通过间接免疫荧光法证实阳性值。我们观察到ANCA阳性UC患者（n = 70）与ANCA阴性对照组（n = 46）相比，DR 2的频率显著增加（44% vs 22%，P = 0.01）。相比之下，ANCA阴性UC病例中DR 2的频率（21%）与对照组（22%，P = 0.9）几乎相同。此外，ANCA阴性UC患者与ANCA阳性UC患者相比，DR 4等位基因增加（P = 0.004）。因此，通过亚临床标志物（ANCA）和分子遗传标志物的组合，已证明UC中存在遗传异质性：ANCA阳性UC与DR 2相关，ANCA阴性UC可能与DR 4相关。
Newly described distinct associations of HLA class II genes with ulcerative colitis (UC) (DR2) and Crohn's disease (CD) (DR1/DQ5) provide strong evidence for genetic heterogeneity of susceptibility between these two forms of inflammatory bowel disease. A familial distribution of antineutrophil cytoplasmic antibodies (ANCAs, a subclinical marker of UC) in UC families has further implied the existence of heterogeneity within UC. To test the hypothesis that the heterogeneity within UC indicated by ANCAs has a genetic basis that resides within the HLA region, we studied 89 UC cases and an ethnically matched control group (n = 50). Serological and molecular typing techniques were applied to define HLA class II genes (DR, DQ). ANCAs were detected using an enzyme-linked immunosorbent assay, and positive values were confirmed by indirect immunofluorescence. We observed that ANCA-positive UC patients (n = 70) had a significantly increased frequency of DR2 compared with ANCA-negative controls (n = 46) (44% vs 22%, P = 0.01). In contrast, the frequency of DR2 in ANCA-negative UC cases (21%) was virtually identical to that in controls (22%, P = 0.9). Furthermore, the ANCA-negative UC patients had an increase in the DR4 allele compared with ANCA-positive UC (P = 0.004). Thus, with the combination of a subclinical marker (ANCAs) and molecular genetic markers, genetic heterogeneity has been demonstrated within UC: ANCA-positive UC associated with DR2, and ANCA-negative UC likely associated with DR4.
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影响因子：
24.5
作者：
YANG, H;MCELREE, C;ROTTER, JI
通讯作者：
ROTTER, JI
犹太人的遗传多样性：DNA 水平的疾病和标记
影响因子：
4
作者：
Alan Emery
通讯作者：
Alan Emery
影响因子：
14.2
作者：
SAXON, A;SHANAHAN, F;TARGAN, S
通讯作者：
TARGAN, S
溃疡性结肠炎中性粒细胞自身抗体：家族聚集和遗传异质性。
影响因子：
29.4
作者：
Shanahan,F;Duerr,RH;Rotter,JI;Yang,H;Sutherland,LR;McElree,C;Landers,CJ;Targan,SR
通讯作者：
Targan,SR
影响因子：
24.5
作者：
CAMBRIDGE, G;RAMPTON, DS;LEAKER, B
通讯作者：
LEAKER, B