HLA DMB1*0101-0101基因型与类风湿关节炎呈正相关。

Positive association of the HLA DMB1*0101-0101 genotype with rheumatoid arthritis.

作者信息

Perdriger A, Guggenbuhl P, Chalès G, Yaouanq J, Quelvennec E, Bonnard M N, Pawlotsky Y, Semana G

机构信息

Department of Rheumatology, Teaching Hospital, Rennes, France.

出版信息

Rheumatology (Oxford). 1999 May;38(5):448-52. doi: 10.1093/rheumatology/38.5.448.

DOI:10.1093/rheumatology/38.5.448

PMID:10371284

Abstract

OBJECTIVE

HLA DM is a non-classical major histocompatibility complex (MHC) class II molecule that has been shown to facilitate peptide loading with classical class II molecules.

METHODS

In this study, we analysed the polymorphism in exon 3 of HLA DMA and DMB genes by a polymerase chain reaction-sequence-specific oligonucleotide probe method in 163 rheumatoid arthritis (RA) patients and 146 ethnically matched controls. The HLA-DRB1 genotype was also analysed by a reverse-dot blot method.

RESULTS

Our results show in RA patients a significant increase in the HLA DMB0101 allele frequency (83% vs 72.3% of the controls, P < 1.6 x 10(-3), significance at P < 0.0125) and in the HLA DMB0101-0101 homozygote genotype frequency [70.8% vs 50% of the controls, P < 4.2 x 10(-4), significance at P < 0.00625, odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.43-4]. The increase in DMB0101 allele and homozygote genotype frequencies was independent of a linkage disequilibrium between DMB and DRB1 alleles. The analysis of non-random associations between the HLA-DM and DRB1 alleles only revealed a significant association in controls between DMB0104 and DRB107 alleles (delta = 0.01, P < 7 x 10(-4), significance at P < 9.6 x 10(-4)). On the other hand, the DMB0101-0102 genotype frequency was increased in DRB1*0401-negative RA patients as compared to controls (11% vs 2%, P < 0.011, significance at P < 0.015, OR = 6.2, 95% CI: 1.2-30).

CONCLUSION

Our data suggest that HLA-DM alleles could play a role in the genetic susceptibility to RA.

摘要

目的

HLA DM是一种非经典的主要组织相容性复合体（MHC）II类分子，已被证明可促进经典II类分子的肽负载。

方法

在本研究中，我们采用聚合酶链反应-序列特异性寡核苷酸探针法，对163例类风湿关节炎（RA）患者和146例种族匹配的对照者的HLA DMA和DMB基因外显子3的多态性进行了分析。还采用反向斑点杂交法分析了HLA-DRB1基因型。

结果

我们的结果显示，RA患者中HLA DMB0101等位基因频率显著增加（83%对对照组的72.3%，P < 1.6 x 10(-3)，在P < 0.0125时有显著性），HLA DMB0101-0101纯合子基因型频率也增加[70.8%对对照组的50%，P < 4.2 x 10(-4)，在P < 0.00625时有显著性，优势比（OR）= 2.4，95%置信区间（CI）：1.43 - 4]。DMB0101等位基因和纯合子基因型频率的增加与DMB和DRB1等位基因之间的连锁不平衡无关。HLA-DM和DRB1等位基因之间的非随机关联分析仅显示，在对照组中DMB0104和DRB107等位基因之间存在显著关联（δ = 0.01，P < 7 x 10(-4)，在P < 9.6 x 10(-4)时有显著性）。另一方面，与对照组相比，DRB10401阴性的RA患者中DMB*0101-0102基因型频率增加（11%对2%，P < 0.011，在P < 0.015时有显著性，OR = 6.2，95% CI：1.2 - 30）。