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Phenotypic variance in childhood coeliac disease and the HLA-DQ/DR dose effect.

Abstract：

OBJECTIVE:Coeliac disease (CD) is associated with HLA-DQ2 and DQ8. The clinical picture is variable and certain human leucocyte antigen (HLA) DQ/DR combinations have a higher relative risk (RR) for CD than others. Moreover, the HLA-DQ gene-dose effect has an impact on the strength of the gluten-specific T-cell response and thus may correlate with clinical presentation and severity of CD. The aim of this study was to determine the correlation between HLA-DQ/DR-based genotypes and the variation in phenotypes of the disease. MATERIAL AND METHODS:A total of 113 non-related Caucasian children clinically diagnosed with CD during the period 1980-2003 with a known HLA type were included in the study. Patients were divided into four categories according to amount of disease expression predisposing to HLA-DQ2 or HLA-DQ8 molecules and the known RR of their HLA-DR/DQ type for CD: high (DR3DQ2 homozygous and DR3DQ2/DR7DQ2), substantial (DR3DQ2/DR5DQ7 and DR5DQ7/DR7DQ2), moderate (DR3DQ2-DR4DQ8 and DR3DQ2/DR*DQ*) and low (DR7DQ2/DR*DQ*, DR4DQ8- DR*DQ* and DR*DQ*- DR*DQ*). The clinical data and HLA genotypes of these patients were compared. RESULTS:The 113 children were diagnosed with CD at a mean age of 4.6 years and boys were significantly older than girls when diagnosed (p=0.01). RR for having CD was highest for the high HLA-risk group (RR 8.1). With the exception of a greater frequency of abdominal distension and fewer non-gastrointestinal symptoms in the substantial HLA-risk group, there were no significant differences in clinical characteristics or degree of severity of the small-bowel histological findings between the children in the different HLA-risk groups. CONCLUSION:No correlation was found between disease severity and a double HLA-DQ2 gene dose.

journal_name

Scand J Gastroenterol

journal_title

Scandinavian journal of gastroenterology

authors

Vermeulen BA,Hogen Esch CE,Yuksel Z,Koning F,Verduijn W,Doxiadis II,Schreuder GM,Mearin ML

doi

10.1080/00365520802116422

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

40-5

issue

1

eissn

0036-5521

issn

1502-7708

pii

904348883

journal_volume

44

pub_type

杂志文章

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