Not all HLA DR3 DQ2 haplotypes confer equal susceptibility to coeliac disease: transmission analysis in families.
BACKGROUND
HLA-DQ is the only established susceptibility factor for coeliac disease. We tested whether all HLA haplotypes with the known risk marker, HLA-DQ2, confer equal susceptibility to coeliac disease, i.e. whether haplotype transmission from DQ2 homozygous parents to patients is random. The random transmission would strengthen the importance of DQ2 as the only risk factor within the HLA region.


METHODS
Inheritance of DQ2-positive haplotypes from parent to patients was investigated in 14 of 127 Finnish coeliac families who had an HLA-DQ2 homozygous parent. HLA alleles and 18 HLA-linked microsatellite markers were used to determine the haplotypes, which were divided into those transmitted and those non-transmitted from DQ2-homozygous parents to patients:


RESULTS
Transmitted haplotypes differed clearly from those not transmitted. The alleles in the transmitted haplotypes were strongly conserved and predominantly consisted of the well-known HLA-A*01, B*08, DRB1*03, DQ2, DPB1*0101 haplotype. The non-transmitted haplotypes, on the other hand, were significantly more heterogeneous; in particular, markers near HLA-A and -B genes differed from the transmitted haplotypes.


CONCLUSIONS
The results suggest that DQ2 is not the only HLA-linked genetic risk factor for coeliac disease but the conserved haplotype harbours at least one other risk gene.
Karell
K
K
Dept of Tissue Typing, Finnish Red Cross Blood Transfusion Service, Helsinki.
Holopainen
P
P
Mustalahti
K
K
Collin
P
P
Mäki
M
M
Partanen
J
J
D000328:Adult; D002446:Celiac Disease / Q000235:genetics*; D002648:Child; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D015803:HLA-DR3 Antigen