Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis.
Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis.
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DOI：
10.1038/gene.2012.17
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发表时间：
2012-09
影响因子：
5
通讯作者：
Seldin, M. F.
中科院分区：
文献类型：
--
作者：
Invernizzi, P.;Ransom, M.;Raychaudhuri, S.;Kosoy, R.;Lleo, A.;Shigeta, R.;Franke, A.;Bossa, F.;Amos, C. I.;Gregersen, P. K.;Siminovitch, K. A.;Cusi, D.;de Bakker, P. I. W.;Podda, M.;Gershwin, M. E.;Seldin, M. F.
原发性胆汁性肝硬化（PBC）的易感性与HLA区域多态性密切相关。为了确定是否可以解释经典的HLA决定因素的协会，我们研究了意大利676例和1440名对照与密集的单核苷酸多态性（SNPs）的经典HLA等位基因和氨基酸的基因分型。虽然以前的全基因组关联研究和我们的结果显示DQB 1附近的SNP关联更强，但我们证明HLA信号可以归因于经典的DRB 1和DPB 1基因。我们的条件分析为DRB 1的主导作用提供了强有力的支持。我们还证明了DPB 1的独立关联。特异性HLA-DRB 1基因（*08、*11和 *14）占DRB 1关联信号的大部分。与先前的研究一致，DRB 1 *08（p = 1.59 × 10−11）是最强的易感等位基因，而DRB 1 *11（p = 1.42 × 10−10）是保护性的。此外，DRB 1 *14和DPB 1关联（DPB 1 *03：01）（p = 9.18 × 10−7）是易感风险等位基因。在HLA 1类或3类区域中未观察到信号。这些发现更好地定义了PBC与HLA的关联，并特别支持经典HLA-DRB 1和DPB 1基因和等位基因在PBC易感性中的作用。
Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with HLA region polymorphisms. To determine if associations can be explained by classical HLA determinants we studied Italian 676 cases and 1440 controls with genotyped with dense single nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (*08, *11 and *14) account for most of the DRB1 association signal. Consistent with previous studies, DRB1*08 (p = 1.59 × 10−11) was the strongest predisposing allele where as DRB1*11 (p = 1.42 × 10−10) was protective. Additionally DRB1*14 and the DPB1 association (DPB1*03:01) (p = 9.18 × 10−7) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC.
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DOI：
10.1111/j.1463-1326.2008.00997.x
发表时间：
2009-02
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Brown WM;Pierce J;Hilner JE;Perdue LH;Lohman K;Li L;Venkatesh RB;Hunt S;Mychaleckyj JC;Deloukas P;Type 1 Diabetes Genetics Consortium
通讯作者：
Type 1 Diabetes Genetics Consortium
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：
3.9
作者：
Kosoy, Roman;Nassir, Rami;Tian, Chao;White, Phoebe A.;Butler, Lesley M.;Silva, Gabriel;Kittles, Rick;Alarcon-Riquelme, Marta E.;Gregersen, Peter K.;Belmont, John W.;De La Vega, Francisco M.;Seldin, Michael F.
通讯作者：
Seldin, Michael F.
影响因子：
3.7
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
通讯作者：
Stankovich J
影响因子：
13.5
作者：
Donaldson, Peter T.;Baragiotta, Anna;Bassendine, Margaret F.
通讯作者：
Bassendine, Margaret F.