B 细胞标记基因多态性与欧洲白种人系统性硬化症关联研究。

Association study of B-cell marker gene polymorphisms in European Caucasian patients with systemic sclerosis.

机构信息

Université Paris Diderot, Hôpital Bichat Claude Bernard, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France.

出版信息

Clin Exp Rheumatol. 2011 Sep-Oct;29(5):839-42. Epub 2011 Oct 31.

PMID:21961844

Abstract

BACKGROUND

BANK1 and BLK B-cell genetic markers have been reproducibly and convincingly found to contribute to susceptibility to systemic sclerosis (SSc).

OBJECTIVES

To determine whether other B-cell genetic markers including CD19, CD20, CD22 and CD24 polymorphisms affect susceptibility to SSc in the European Caucasian population.

METHODS

A case-control study was performed in 900 patients with SSc and 1034 healthy controls. Among the whole SSc population, 304 (34%) had the diffuse cutaneous subtype, 551 (61%) had the limited cutaneous subtype, 732 (81%) were positive for antinuclear antibodies , 331 (37%) were positive for anticentromere antibodies and 228 (25%) for the topo-isomerase I. Genotyping has been performed for CD19 rs35979293, CD19 rs2904880, CD20 rs7126354, CD20 rs3802954, CD20 rs105146, CD20 rs4939364, CD22 rs10406069, CD22 rs10413500, CD22 rs10419538, CD22 rs34826052 and CD24 ins-del polymorphisms.

RESULTS

Genotype frequencies were at the Hardy-Weinberg equilibrium in the control population for all the SNPs investigated and observed frequencies were very similar to those expected in the European population. Allelic and genotypic frequencies for all these tested SNPs were found to be similar in SSc patients and controls. Moreover, subphenotype analyses in particular for subgroups having the diffuse cutaneous subset or topo-isomerase I positive antibodies, which are the most associated with BANK1 variants, did not detect any difference between SSc patients and controls.

CONCLUSIONS

These results obtained through a large cohort of European caucasian patients with SSc do not support the contribution of CD19, CD20, CD22, CD24 variants to the genetic susceptibility of SSc.

摘要

背景

BANK1 和 BLK B 细胞遗传标志物已被反复且令人信服地证明与系统性硬化症（SSc）的易感性有关。

目的

确定其他 B 细胞遗传标志物，包括 CD19、CD20、CD22 和 CD24 多态性是否会影响欧洲白种人群中 SSc 的易感性。

方法

在 900 例 SSc 患者和 1034 例健康对照中进行病例对照研究。在整个 SSc 人群中，304 例（34%）为弥漫性皮肤亚型，551 例（61%）为局限性皮肤亚型，732 例（81%）抗核抗体阳性，331 例（37%）抗着丝点抗体阳性，228 例（25%）拓扑异构酶 I 阳性。对 CD19 rs35979293、CD19 rs2904880、CD20 rs7126354、CD20 rs3802954、CD20 rs105146、CD20 rs4939364、CD22 rs10406069、CD22 rs10413500、CD22 rs10419538、CD22 rs34826052 和 CD24 ins-del 多态性进行了基因分型。

结果

所有研究的 SNP 在对照组中的基因型频率均处于哈迪-温伯格平衡状态，观察到的频率与欧洲人群中的预期频率非常相似。在 SSc 患者和对照组中，所有这些测试 SNP 的等位基因和基因型频率均相似。此外，对具有弥漫性皮肤亚型或拓扑异构酶 I 阳性抗体的亚表型分析，特别是与 BANK1 变异最相关的亚组，未发现 SSc 患者与对照组之间存在任何差异。