Celiac disease and human leukocyte antigen genotype: Accuracy of diagnosis in self-diagnosed individuals, dosage effect, and sibling risk

被引:17
作者
Lewis, C
Book, L
Black, J
Sawitzke, A
Cannon-Albright, L
Zone, J
Neuhausen, S
机构
[1] Univ Utah, Sch Med, Dept Med Informat, Div Genet Epidemiol, Salt Lake City, UT 84108 USA
[2] Univ Utah, Sch Med, Dept Internal Med, Div Rheumatol, Salt Lake City, UT 84108 USA
[3] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT 84108 USA
[4] Univ Utah, Sch Med, Dept Pediat, Div Pediat Gastroenterol & Nutr, Salt Lake City, UT 84108 USA
[5] Kings Coll London, Guys Kings & St Thomass Sch Med, Div Med & Mol Genet, London WC2R 2LS, England
关键词
celiac disease; dermatitis herpetiformis; DQ2; genetics; gluten-sensitive enteropathy; HLA genotypes;
D O I
10.1097/00005176-200007000-00007
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Celiac disease is an autoimmune disorder of the small intestine characterized by intolerance to gluten. Traditionally. diagnosis is made by intestinal biopsy. Testing for immunoglobulin (Ig) A endomysial antibodies in the serum also is used for diagnosis. Biopsy and serology revert to normal with adherence to a gluten-free diet. Often, after an index case is diagnosed, siblings with symptoms adhere to a gluten-free diet without biopsy or serologic confirmation. More than 90% of patients with celiac disease have the human leukocyte antigen (HLA) DQA1*0501-DQB1*0201 genotype. Non-HLA genes also have been implicated. Methods: One hundred ninety-five individuals with confirmed or suspected celiac disease were identified in 73 families affected by the disease. IgA endomysial antibody testing was performed for all symptomatic family members who did not have biopsy-confirmed diagnoses. DNA samples were genotyped at D6S276 and the HLA class II loci DQA and DQB. Results: At the time sampling was begun in families, 88 of 177 (49.7%) individuals were self-diagnosed and adhering to a gluten-free diet. Ninety percent (91/101) of confirmed cases (biopsy or serology) had at least 1 copy of the DQA1*0501-DQB1*0201 genotype, whereas only 67% (46/69) of cases self-diagnosed (adherence to gluten-free diet without confirmation) had at least 1 copy. Of confirmed cases, 61% carried two copies of DQB*0201. It is estimated that the HLA association and other unlinked genes contribute approximately equally to the sibling risk of celiac disease. Conclusions: A dosage effect of DQB1*0201 may be associated with an increased risk of celiac disease. Self-diagnosis of celiac disease is as common as confirmed diagnosis in families in the United States. Diagnosis of celiac disease on the basis of clinical response to gluten restriction is inaccurate. With long-term adherence to a gluten-free diet, serologic test results are likely to be negative. Based on HLA genotype, approximately one third of self-diagnosed individuals are unlikely to have celiac disease. However, it is not possible to determine which individuals consuming a gluten-free diet have the disease. Therefore, before starting a gluten-free diet, serologic screening and biopsy confirmation are necessary.
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页码:22 / 27
页数:6
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