Mode of inheritance of HLA-DRB1 shared epitope in Japanese familial rheumatoid arthritis.
OBJECTIVE
To clarify the mode of genetic contribution of the HLA-DR shared epitope (SE) to the pathogenesis of familial cases of Japanese rheumatoid arthritis (RA).


METHODS
Fifty-three unrelated Japanese RA families that had more than 2 affected sibs were selected. The HLA-DR shared epitope typing was carried out by the PCR method and PCR-SSCP (single stranded DNA conformation polymorphism) method. Affected sib pair analysis was carried out using the MAPMAKER/SIB 2.0 program. The mode of inheritance was also calculated based on the sharing of genes identical by descent (IBD) between siblings in each of the 53 affected sib-pairs (propositus and the 2nd affected sib).


RESULTS
The maximum LOD score of HLA-DR was 0.437, and the sharing of 2 IBDs, 1 IBD, and no IBDs between affected sibs were 0.330, 0.500, and 0.170, respectively. The sharing distribution of IBD was confirmed to be compatible with the dominant or additive mode since the observed gene frequency of SE was 0.255.


CONCLUSIONS
The HLA-DR shared epitope participated in the pathogenesis of familial cases of Japanese RA. The SE contributes to this pathogenesis in either the dominant or additive mode of inheritance.
Takeuchi
F
F
Dept. of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan. fujio-tky@umin.ac.jp
Mori
M
M
Goto
M
M
Matsuta
K
K
Yamada
A
A
Chihara
T
T
Hanyu
T
T
Murayama
T
T
Yamamoto
S
S
Takubo
N
N
Murata
N
N
Matsubara
T
T
Itakura
M
M
Sakuta
H
H
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002648:Child; D000939:Epitopes / Q000235:genetics*; D005192:Family Health; D005799:Genes, Dominant; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007564:Japan
D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains