一项关于多发性硬化易感性与2号染色体q33区域的两阶段研究。

A two-stage study on multiple sclerosis susceptibility and chromosome 2q33.

作者信息

Bonetti A, Reunanen K, Finnilä S, Koivisto K, Wikström J, Sumelahti M-L, Pirttilä T, Elovaara I, Reunanen M, Saarela J, Peltonen L, Rantamäki T, Tienari P J

机构信息

Department of Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki University Central Hospital, Haartmaninkatu 4, Helsinki, Finland.

出版信息

Genes Immun. 2004 Mar;5(2):142-6. doi: 10.1038/sj.gene.6364049.

DOI:10.1038/sj.gene.6364049

PMID:14724692

Abstract

We have performed a two-stage study to analyse the association of polymorphism on chromosome 2q33 with multiple sclerosis (MS). In all, 17 markers were analysed in stage-1 in 134 Finnish MS families and the observed associations were tested in stage-2 in 186 MS families. We did not find previously reported allelic or haplotype associations with CTLA4. We obtained a weak signal of two distinct predisposing genes, one proximal the other distal of CTLA4. The putative proximal gene was associated with the marker rs3977 in families lacking HLA-DR2 (P=0.02 and 0.02) and the other distal gene was associated with D2S1271 in families from a high-risk region in western Finland (P=0.02 and 0.01). Based on the >3 cM distance and the lack of linkage disequilibrium between these loci, we conclude that the two association signals are independent. Our results provide preliminary evidence for two distinct MS susceptibility genes on 2q33 outside of CTLA4.

摘要

我们开展了一项两阶段研究，以分析2q33染色体上的多态性与多发性硬化症（MS）之间的关联。在第一阶段，对134个芬兰MS家系中的17个标记进行了分析，并在第二阶段对186个MS家系中观察到的关联进行了检验。我们未发现先前报道的与CTLA4的等位基因或单倍型关联。我们获得了两个不同的易感基因的微弱信号，一个在CTLA4近端，另一个在其远端。假定的近端基因在缺乏HLA-DR2的家系中与标记rs3977相关（P = 0.02和0.02），另一个远端基因在芬兰西部高危地区的家系中与D2S1271相关（P = 0.02和0.01）。基于这些位点之间大于3 cM的距离以及连锁不平衡的缺乏，我们得出结论，这两个关联信号是独立的。我们的结果为CTLA4之外2q33上两个不同的MS易感基因提供了初步证据。