HLA-DR genotypes in familial rheumatoid arthritis: increased frequency of protective and neutral alleles in a multicase family.
OBJECTIVE
We describe a unique family where each of the 5 siblings in the second generation has rheumatoid arthritis (RA). Two other members of the family have RA and systemic lupus erythematosus (SLE), respectively. No members of previous generations in the family had documented inflammatory arthritis. Due to the suspected genetic predisposition, HLA-DR genotypes were determined in the affected siblings and their parents, children, and grandchildren. We investigated the possible role of various HLA-DR alleles in the evolution of RA in this multicase family.


METHODS
HLA-DRB1* alleles were determined by polymerase chain reaction using the sequence-specific primer-Olerup method.


RESULTS
The most common alleles in the 6 persons with RA were HLA-DRB1*07 and DRB1*15, which are known to be protective and neutral in RA. No patient or family member carried any HLA-DR4 alleles.


CONCLUSIONS
HLA-DRB1*07 and DRB1*15 alleles are thought to be protective or neutral in RA. However, the majority of RA patients in the family and nearly half of all family members carried these alleles, suggesting a role of these genotypes in susceptibility to RA. No RA patient in this family carried HLA-DR4 alleles. Thus, in our rare family with 6 RA cases, an unexpected genetic background may be involved in the increased susceptibility to inflammatory arthritis.
Zsilák
Szilvia
S
National Institute of Rheumatology and Physiotherapy, Budapest, Hungary. zsilaksz@freemail.hu
Gál
János
J
Hodinka
László
L
Rajczy
Katalin
K
Balog
Attila
A
Sipka
Sándor
S
Baráth
Sándor
S
Kapitány
Anikó
A
Zilahi
Erika
E
Szekanecz
Zoltán
Z
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C456920:HLA-DRB1*07 antigen; C507799:HLA-DRB1*15 antigen