A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis.
A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis.
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DOI：
10.1371/journal.pone.0013454
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发表时间：
2010-10-26
期刊：
影响因子：
3.7
通讯作者：
Stankovich J
中科院分区：
文献类型：
--
作者：
Field J;Browning SR;Johnson LJ;Danoy P;Varney MD;Tait BD;Gandhi KS;Charlesworth JC;Heard RN;Australia and New Zealand Multiple Sclerosis Genetics Consortium;Stewart GJ;Kilpatrick TJ;Foote SJ;Bahlo M;Butzkueven H;Wiley J;Booth DR;Taylor BV;Brown MA;Rubio JP;Stankovich J
我们进行了一项人类白细胞抗原（HLA）复合物的关联研究，以确定与多发性硬化症（MS）相关的位点。比较1618例MS病例和3413例欧洲血统对照中的1927个SNP，我们确定了7个SNP与MS独立相关，条件是其他（每个）。所有相关性在2212例病例和2251例对照的独立重复队列中均显著（），在联合数据集中高度显著（）。相关的SNPs包括HLA-DRB 1 *15：01和HLA-DRB 1 *03：01的替代物，以及与HLA-A*02：01、HLA-DRB 1 *04：01和HLA-DRB 1 *13：03处于中度连锁不平衡（LD）的SNPs。我们还发现了与II类基因HLA-DPB 1中的rs 9277535的强关联（发现集，复制集，组合）。HLA-DPB 1位于更常见的II类基因HLA-DRB 1、-DQA 1和-DQB 1的着丝粒。它通过重组热点与这些基因分开，并且这种关联不受DRB 1、DQA 1和DQB 1基因型条件的影响。因此，rs 9277535代表了一个独立的MS易感基因座的全基因组意义。它与HLA-DPB 1 *03：01等位基因相关，该等位基因之前在较小的研究中与MS有关。需要在大数据集中进行进一步的基因分型以确认和解决这种关联。
We conducted an association study across the human leukocyte antigen (HLA) complex to identify loci associated with multiple sclerosis (MS). Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each ). All associations were significant in an independent replication cohort of 2212 cases and 2251 controls () and were highly significant in the combined dataset (). The associated SNPs included proxies for HLA-DRB1*15:01 and HLA-DRB1*03:01, and SNPs in moderate linkage disequilibrium (LD) with HLA-A*02:01, HLA-DRB1*04:01 and HLA-DRB1*13:03. We also found a strong association with rs9277535 in the class II gene HLA-DPB1 (discovery set , replication set , combined ). HLA-DPB1 is located centromeric of the more commonly typed class II genes HLA-DRB1, -DQA1 and -DQB1. It is separated from these genes by a recombination hotspot, and the association is not affected by conditioning on genotypes at DRB1, DQA1 and DQB1. Hence rs9277535 represents an independent MS-susceptibility locus of genome-wide significance. It is correlated with the HLA-DPB1*03:01 allele, which has been implicated previously in MS in smaller studies. Further genotyping in large datasets is required to confirm and resolve this association.
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影响因子：
5
作者：
Bergamaschi, L.;Leone, M. A.;D'Alfonso, S.
通讯作者：
D'Alfonso, S.
影响因子：
3.7
作者：
Cree BA;Rioux JD;McCauley JL;Gourraud PA;Goyette P;McElroy J;De Jager P;Santaniello A;Vyse TJ;Gregersen PK;Mirel D;Hafler DA;Haines JL;Pericak-Vance MA;Compston A;Sawcer SJ;Oksenberg JR;Hauser SL;IMAGEN;IMSGC
通讯作者：
IMSGC
影响因子：
3.5
作者：
Bronson, Paola G.;Caillier, Stacy;Barcellos, Lisa F.
通讯作者：
Barcellos, Lisa F.
DOI：
10.1038/ejhg.2009.41
发表时间：
2009-10
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.5
作者：
Fernando MM;Stevens CR;Walsh EC;De Jager PL;Goyette P;Plenge RM;Vyse TJ;Rioux JD
通讯作者：
Rioux JD