Gene dose effect of the DQB1*0201 allele contributes to severity of coeliac disease.
OBJECTIVE
Coeliac disease (CD) susceptibility has been shown to be associated with the HLA alleles DQA1*0501 and DQB1*0201. This HLA-associated risk has been estimated to account for 29-40% of the genetic component of CD. Conflicting data have been published on the gene dose effect of these HLA alleles on the risk and severity of CD. In this study the aim was to investigate the association between the number of HLA risk alleles and the severity of CD.


METHODS
Fifty-four Finnish CD families, including 144 CD patients mainly diagnosed in adulthood (94.4%), were enrolled in the study. The association between the number of DQA1*0501 and DQB1*0201 alleles and villous atrophy, symptoms and laboratory parameters at the time of diagnosis, and the association with villous atrophy after one year of treatment on a gluten-free diet were studied.


RESULTS
The homozygosity for the DQB1*0201 allele was associated with a more severe form of CD assessed by more severe villous atrophy (p=0.011), younger age (p=0.036), more severe diarrhoea (p=0.048) and a lower level of blood haemoglobin at the time of diagnosis (p=0.010). Furthermore, the homozygosity for the DQB1*0201 allele was associated with a slower recovery of villous atrophy after a gluten-free diet (p=0.041). In contrast, the DQA1*0501 allele did not have a significant association with the severity of CD.


CONCLUSIONS
Our results demonstrate a gene dose effect of the DQB1*0201 allele on the clinical heterogeneity of CD and on the rate of recovery from villous atrophy in patients on a gluten-free diet.
Department of Medicine, University of Kuopio, Kuopio, Finland.
Hannele
H
Karinen
Päivi
P
Kärkkäinen
Jussi
J
Pihlajamäki
Esko
E
Janatuinen
Markku
M
Heikkinen
Risto
R
Julkunen
Veli-Matti
VM
Kosma
Anita
A
Naukkarinen
Markku
M
Laakso
D000328:Adult; D000483:Alleles; D001706:Biopsy; D002446:Celiac Disease / Q000178:diet therapy / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D004247:DNA