纤连蛋白基因多态性与II型混合性冷球蛋白血症中B细胞淋巴瘤的发生有关。

Fibronectin gene polymorphisms are associated with the development of B-cell lymphoma in type II mixed cryoglobulinemia.

作者信息

Fabris M, Quartuccio L, Salvin S, Pozzato G, De Re V, Mazzaro C, Ferri C, Baldini C, De Vita S

机构信息

Clinic of Rheumatology, DPMSC, School of Medicine, University of Udine, 33100 Udine, Italy.

出版信息

Ann Rheum Dis. 2008 Jan;67(1):80-3. doi: 10.1136/ard.2006.067637. Epub 2007 May 25.

DOI:10.1136/ard.2006.067637

PMID:17526550

Abstract

OBJECTIVE

To analyse fibronectin (FN) gene polymorphisms in type II mixed cryoglobulinemic syndrome (MCsn), an immune-complex mediated systemic vasculitis linked to hepatitis C virus (HCV) infection and characterised by rheumatoid factor (RF) positive B-cell proliferation at high risk for the progression into non-Hodgkin's lymphoma (NHL).

METHODS

Samples from 74 patients with MCsn (type II serum cryoglobulins and clinical signs of vasculitis) were studied. In all, 58 (78.4%) patients were HCV-positive. In total, 21 (28.4%) patients developed a B-cell NHL during the course of MCsn. A total of 72 patients with HCV-negative and MC-unrelated NHL and 110 healthy blood donors (HBDs) were taken as controls. HaeIIIb and MspI FN gene polymorphisms were analysed by PCR and specific restriction enzyme digestions, following reported procedures. Plasma FN levels were analysed by ELISA, whenever possible.

RESULTS

HaeIIIb and MspI allele and genotype frequencies did not differ between MCsn patients and HBDs. Of note, the DD-MspI (OR = 5.99; CI 1.77-20.261, p = 0.0039) and the AA-HaeIIIb (OR = 4.82, CI 1.42-16.39, p = 0.0176) homozygosis appeared significantly associated with the development of B-cell NHL in MCsn patients, with the HaeIIIb A allele possibly conferring an increased risk of NHL in the general population (OR = 1.72, CI 1.128-2.635, p = 0.0133). None of the other MCsn-related clinical manifestations were significantly associated with a particular genetic pattern. No association between FN plasma levels and FN genotypes was found.

CONCLUSION

Genotyping for MspI and HaeIIIb FN gene polymorphisms may be clinically relevant to define the risk of lymphoma development in MCsn.

摘要

目的

分析II型混合性冷球蛋白血症（MCsn）中的纤连蛋白（FN）基因多态性。MCsn是一种免疫复合物介导的系统性血管炎，与丙型肝炎病毒（HCV）感染相关，其特征为类风湿因子（RF）阳性的B细胞增殖，具有进展为非霍奇金淋巴瘤（NHL）的高风险。

方法

研究了74例MCsn患者（II型血清冷球蛋白和血管炎临床体征）的样本。其中，58例（78.4%）患者HCV呈阳性。共有21例（28.4%）患者在MCsn病程中发生了B细胞NHL。选取72例HCV阴性且与MC无关的NHL患者和110名健康献血者（HBD）作为对照。按照报道的程序，通过PCR和特异性限制性酶切分析HaeIIIb和MspI FN基因多态性。尽可能通过ELISA分析血浆FN水平。

结果

MCsn患者与HBD之间HaeIIIb和MspI等位基因及基因型频率无差异。值得注意的是，DD-MspI（OR = 5.99；CI 1.77 - 20.261，p = 0.0039）和AA-HaeIIIb（OR = 4.82，CI 1.42 - 16.39，p = 0.0176）纯合子与MCsn患者B细胞NHL的发生显著相关，HaeIIIb A等位基因可能使一般人群患NHL的风险增加（OR = 1.72，CI 1.128 - 2.635，p = 0.0133）。其他与MCsn相关的临床表现均与特定的遗传模式无显著关联。未发现血浆FN水平与FN基因型之间存在关联。