Toda Y, Minamikawa Y, Akagi S, Sugano H, Mori Y, Nishimura H, Arita S, Sugino Y, Ogawa R
Department of Orthopaedic Surgery, Kansai Medical University, Otokoyama Hospital, Kyoto, Japan.
Ann Rheum Dis. 1994 Sep;53(9):587-92. doi: 10.1136/ard.53.9.587.
To assess the relationship between HLA-DRB1 genotypes and the progression of bone destruction in Japanese patients with RA.
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.
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.
Genotyping of HLA-DRB1 can be a useful prognostic marker in the early phase of RA.
评估日本类风湿关节炎（RA）患者中HLA - DRB1基因型与骨破坏进展之间的关系。
采用聚合酶链反应和等位基因特异性寡核苷酸探针技术，对160例日本RA患者的HLA - DRB1等位基因进行检测。根据既往报道，将HLA - DR 0101、0401、0404、0405、1001和1402视为RA的易感等位基因。根据患者拥有两个、一个或没有易感因素，将患者分为三组（S/S组、S/N组和N/N组）。采用Larsen标准评估手腕和手指的放射学改变分级。首先在160例横断面病例中比较放射学分级与基因分型结果。然后对从用于横断面研究的160例病例中选取的57例病例组成的亚组进行回顾性研究。
在160例横断面病例中，表达骨破坏阶段与RA病程关系的散点图中，在骨破坏发展的早期阶段，回归线和95%置信区间将S/S组与S/N组和N/N组区分开来。在对57例病例的回顾性研究中，症状出现后手腕发展到V期的中位年数，S/S组患者为13.1年，S/N组为22.7年，N/N组为23.0年。S/S组与S/N组之间以及S/S组与N/N组之间观察到的差异具有统计学意义（p < 0.01），但S/N组与N/N组之间的差异无统计学意义。因此，S/S组手腕和手指的骨破坏进展比S/N组和N/N组更快；在手腕和手指骨破坏进展过程中，HLA - DRB1的类风湿易感等位基因相对于非易感等位基因可被认为是遗传隐性的。
HLA - DRB1基因分型可作为RA早期阶段有用的预后标志物。
