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法国东部HLA-DM基因与类风湿性关节炎的关联

The association of HLA-DM genes with rheumatoid arthritis in Eastern France.

作者信息

Toussirot E, Sauvageot C, Chabod J, Ferrand C, Tiberghien P, Wendling D

机构信息

Department of Rheumatology, University Hospital Jean Minjoz, Besançon cédex, France.

出版信息

Hum Immunol. 2000 Mar;61(3):303-8. doi: 10.1016/s0198-8859(99)00126-3.

Abstract

In this study, the polymorphisms of the HLA DMA and DMB genes in patients with rheumatoid arthritis (RA) were examined.DMA and DMB typing was performed in 120 white RA patients from eastern France and 100 healthy controls, using PCR-SSO (sequence specific oligonucleotide probes) method for DMA determination and PCR-RFLP (restriction fragment length polymorphism) method for DMB typing. All patients and controls had been HLA DRB1* genotyped.DMA0103 was found significantly increased in RA patients (RA vs. controls: 18.3% vs. 4%) (p(corr) = 0.004; OR: 5.39; CI: 1.67-19.23). A decreased frequency of DMA0102 was also observed in the RA group (RA vs. controls: 18.3% vs. 31%), but not significantly. There were no differences in the prevalence of DMB alleles between RA and controls. The patients and the controls were then stratified according to the expression of the HLA DRB1* RA-linked alleles (DRB101 and 04) and this allowed us to find no linkage disequilibrium between DMA0103 and DRB101 or 04 alleles. Finally, most DMA0103 patients were positive for rheumatoid factors and had extraarticular involvement such as subcutaneous nodules. Thus, our results suggest that DMA*0103 could be an additional genetic factor for RA susceptibility in French whites.

摘要

在本研究中,对类风湿关节炎(RA)患者的HLA DMA和DMB基因多态性进行了检测。采用PCR - SSO(序列特异性寡核苷酸探针)法对来自法国东部的120例白人RA患者和100例健康对照进行DMA分型,采用PCR - RFLP(限制性片段长度多态性)法对DMB进行分型。所有患者和对照均已进行HLA DRB1基因分型。发现RA患者中DMA0103显著增加(RA组与对照组:18.3%对4%)(校正p值 = 0.004;OR:5.39;CI:1.67 - 19.23)。在RA组中也观察到DMA0102频率降低(RA组与对照组:18.3%对31%),但无统计学意义。RA组和对照组之间DMB等位基因的患病率无差异。然后根据HLA DRB1 RA相关等位基因(DRB101和04)的表达对患者和对照进行分层,结果发现DMA0103与DRB101或04等位基因之间无连锁不平衡。最后,大多数DMA0103患者类风湿因子呈阳性,并有皮下结节等关节外表现。因此,我们的结果表明,DMA*0103可能是法国白人RA易感性的一个额外遗传因素。

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