HLA DQ gene dosage and risk and severity of celiac disease.
OBJECTIVE
Celiac 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.


METHODS
High-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.


RESULTS
Ninety-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.


CONCLUSIONS
Both 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.
Murray
Joseph A
JA
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. murray.joseph@mayo.edu
Moore
S Breanndan
SB
Van Dyke
Carol T
CT
Lahr
Brian D
BD
Dierkhising
Ross A
RA
Zinsmeister
Alan R
AR
Melton
L Joseph
LJ
Kroning
Cynthia M
CM
El-Yousseff
Mounif
M
Czaja
Albert J
AJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002446:Celiac Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008910:Minnesota; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D004247:DNA