Tuokko J, Nejentsev S, Luukkainen R, Toivanen A, Ilonen J
Department of Medical Microbiology, University of Turku, Finland.
Arthritis Rheum. 2001 Feb;44(2):315-22. doi: 10.1002/1529-0131(200102)44:2<315::AID-ANR48>3.0.CO;2-G.
To further characterize the HLA gene products that play an important role in the pathogenesis of rheumatoid arthritis (RA).
One hundred thirty-four haplotypes from 67 Finnish RA patients and 77 control haplotypes were analyzed for HLA-DRB1 loci, associated alleles of the HLA-DQB1 locus, alleles of the type 2 transporter-associated antigen processing (TAP2) genes, and HLA-B27. In addition, a panel of microsatellite markers within the HLA class I and class III regions was studied.
The frequency of HLA-DRB104 in the haplotypes of RA patients was found to be 34% (45 of 134) compared with 14% (10 of 72) in control haplotypes (P = 0.004). The frequency of HLA-DRB113 was decreased in RA haplotypes (4%, or 5 of 134) in contrast to control haplotypes (24%, or 17 of 72) (P = 0.000031). The decrease in DRB113 was not secondary to the increase in DRB104, since it was also found among DRB104-negative haplotypes (P < 0.001). The DRB113-associated DQB1*0604 allele was similarly decreased in RA haplotypes (P = 0.025). The TAP2I allele of I/J dimorphism was increased in RA patients (85%, or 114 of 134) as compared with controls (69%, or 49 of 71) (P = 0.011). Of the tumor necrosis factor (TNF) microsatellite alleles, TNFa6 and TNFb5 were found to be increased in RA haplotypes (for a6 27% versus 5% in controls [P = 0.00043], and for b5 43% versus 26% in controls [P = 0.037]).
Both protection-associated and susceptibility-associated alleles can be found among HLA class II genes, and the results suggest that loci outside DR/DQ may contribute to the pathogenesis of RA.
进一步鉴定在类风湿关节炎（RA）发病机制中起重要作用的HLA基因产物。
分析了67例芬兰RA患者的134个单倍型和77个对照单倍型的HLA-DRB1基因座、HLA-DQB1基因座的相关等位基因、2型转运体相关抗原加工（TAP2）基因的等位基因以及HLA-B27。此外，还研究了HLA I类和III类区域内的一组微卫星标记。
发现RA患者单倍型中HLA-DRB104的频率为34%（134个中的45个），而对照单倍型中为14%（72个中的10个）（P = 0.004）。与对照单倍型（24%，即72个中的17个）相比，RA单倍型中HLA-DRB113的频率降低（4%，即134个中的5个）（P = 0.000031）。DRB113的降低并非继发于DRB104的增加，因为在DRB104阴性单倍型中也发现了这种情况（P < 0.001）。与DRB113相关的DQB1*0604等位基因在RA单倍型中同样降低（P = 0.025）。与对照组（69%，即71个中的49个）相比，RA患者中I/J二态性的TAP2I等位基因增加（85%，即134个中的114个）（P = 0.011）。在肿瘤坏死因子（TNF）微卫星等位基因中，发现TNFa6和TNFb5在RA单倍型中增加（a6在对照组中为5%，在RA中为27% [P = 0.00043]；b5在对照组中为26%，在RA中为43% [P = 0.037]）。
在HLA II类基因中可发现与保护相关和与易感性相关的等位基因，结果表明DR/DQ以外的基因座可能参与RA的发病机制。
