HLA DQ gene dosage and risk and severity of Celiac disease
HLA DQ gene dosage and risk and severity of Celiac disease
复制标题
DOI：
10.1016/j.cgh.2007.08.013
复制
发表时间：
2007-12-01
影响因子：
12.6
通讯作者：
Czaja, Albert J.
中科院分区：
文献类型：
--
作者：
Murray, Joseph A.;Moore, S. Breanndan;Czaja, Albert J.
背景与目的：腹腔疾病(CD)是一种与DQA和DQB基因编码的某些人类白细胞抗原分子密切相关的慢性小肠炎症性疾病。本研究的目的是检测DQA和DQB等位基因在美国人群中决定CD发病风险、发病年龄和严重程度的作用。方法对84名明尼苏达州东南部CD患者和102名对照人群进行高分辨率第二类人类白细胞抗原基因分型，以确定DQA和DQB等位基因对疾病风险的贡献。结果97%的CD患者同时携带DQA1*05和DQB1*02两种等位基因。携带DQB1*02第二个等位基因的人患CD的可能性是只携带一个等位基因的人的5倍(95%可信区间，1.4-18.1)。结论人类白细胞抗原DQA1*05和DQB1*02等位基因均与CD发病风险显著相关，但DQB1*02的作用更大。携带2个DQB1*02拷贝与更高的患病风险相关，但不能预测更早的发病年龄和诊断或疾病严重程度。评估DQB1*02等位基因的拷贝数可能允许对疾病风险进行分层。
Background & AimsCeliac disease (CD) is a chronic inflammatory disorder of the small intestine that is strongly associated with certain HLA molecules encoded by DQA and DQB genes. The aim of this study was to examine the role of DQA and DQB alleles in determining the risk for and the age of onset and severity of CD in an American population.MethodsHigh-resolution class 2 HLA genotyping was performed in a population-based sample (n = 84) of southeastern Minnesota residents with CD and a comparable control group (n = 102) to determine the contribution of DQA and DQB alleles to disease risk. Logistic regression modeling was used to examine the relative and absolute risks of CD.ResultsNinety-seven percent of CD patients carried both of the HLA alleles, DQA1*05 and DQB1*02. Those who carried a second allele of DQB1*02 were 5 times more likely to have CD than those with just one (95% confidence interval, 1.4–18.1). The carriage of 2 copies of DQB1*02 did not predict either an earlier age of onset or severity of disease.ConclusionsBoth HLA alleles DQA1*05 and DQB1*02 are associated with a greatly increased risk of CD, although the latter has the greater effect. Carrying 2 copies of DQB1*02 was associated with an even greater risk for disease but did not predict an earlier age of onset and diagnosis or disease severity. Assessing the copy number of the DQB1*02 allele might allow for the stratification of disease risk.