Rheumatoid-susceptible alleles of HLA-DRB1 are genetically recessive to non-susceptible alleles in the progression of bone destruction in the wrists and fingers of patients with RA.
OBJECTIVE
To assess the relationship between HLA-DRB1 genotypes and the progression of bone destruction in Japanese patients with RA.


METHODS
The HLA-DRB1 alleles were determined by polymerase chain reaction and allele specific oligonucleotide probe techniques in 160 Japanese patients with RA. HLA-DR 0101, 0401, 0404, 0405, 1001 and 1402 were regarded as susceptible alleles of RA according to previous reports. Patients were classified into three groups (S/S, S/N and N/N group), based on the possession of two, one or no susceptible factor. The grading of radio-graphic changes in the wrists and fingers were evaluated by Larsen's criteria. The radiographic grades were first compared with the results of genotyping in the 160 cross sectional cases. A retrospective study was then conducted on a subgroup consisting of 57 cases taken from the 160 cases used for the cross sectional study.


RESULTS
In the scatter diagram of the 160 cross sectional cases expressing the relationship between the stage of bone destruction and duration of RA, the regression line and the 95% confidence intervals separated the S/S group from the S/N and N/N groups in the early phase of development of bone destruction. In the retrospective study on the 57 cases the median years taken to development to stage V in the wrists after the onset of symptoms were 13.1 in the patients in the S/S group, 22.7 in the S/N group and 23.0 in the N/N group. The difference observed between the S/S and S/N group, and between the S/S and N/N group were statistically significant (p < 0.01), but that between the S/N and N/N groups was not. Thus the bone destruction in the wrists and fingers progressed more rapidly in the S/S group than in the S/N and N/N groups; and the rheumatoid susceptible alleles of HLA-DRB1 can be considered to be genetically recessive to the non-susceptible alleles in the progression of bone destructions in the wrists and fingers.


CONCLUSIONS
Genotyping of HLA-DRB1 can be a useful prognostic marker in the early phase of RA.
Department of Orthopaedic Surgery, Kansai Medical University, Otokoyama Hospital, Kyoto, Japan.
Y
Y
Toda
Y
Y
Minamikawa
S
S
Akagi
H
H
Sugano
Y
Y
Mori
H
H
Nishimura
S
S
Arita
Y
Y
Sugino
R
R
Ogawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000473:pathology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005384:Finger Joint; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors; D014955:Wrist Joint
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains