Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A.
Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A.
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DOI：
10.1038/nature06406
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发表时间：
2007-12-06
期刊：
影响因子：
64.8
通讯作者：
Todd, John A.
中科院分区：
文献类型：
--
作者：
Nejentsev, Sergey;Howson, Joanna M. M.;Walker, Neil M.;Szeszko, Jeffrey;Field, Sarah F.;Stevens, Helen E.;Reynolds, Pamela;Hardy, Matthew;King, Erna;Masters, Jennifer;Hulme, John;Maier, Lisa M.;Smyth, Deborah;Bailey, Rebecca;Cooper, Jason D.;Ribas, Gloria;Campbell, R. Duncan;Clayton, David G.;Todd, John A.
6号染色体上的主要组织相容性复合体（MHC）与比人类基因组的任何其他区域更常见的疾病的易感性相关，包括几乎所有被归类为自身免疫性疾病的疾病。在1型糖尿病中，主要的遗传易感性决定因素已被定位于MHC II类基因HLA-DQB 1和HLA-DRB 1（参考文献），但这些基因不能完全解释1型糖尿病与MHC区域之间的关联。由于该地区极端的基因密度，疾病相关等位基因的多样性，等位基因之间的强关联，有限的基因分型能力，以及统计方法和样本量不足，MHC内哪些以及有多少位点决定易感性仍不清楚。在这里，在几个大的1型糖尿病数据集中，我们分析了总共1,729个多态性，并应用统计方法-递归分割和回归-来确定疾病对MHC I类基因HLA-B和HLA-A的易感性（风险比>1.5; P组合分别为2.01×10-19和2.35×10-13）。其他具有较小和/或罕见效应的位点也可能涉及，但为了找到这些位点，未来的搜索必须考虑HLA II类和I类基因，并使用更大的样本。结合以前的研究，我们得出结论，MHC-I类介导的事件，主要涉及HLA-B*39，有助于1型糖尿病的病因。
The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region’s extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression—to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios>1.5; Pcombined=2.01×10-19 and 2.35×10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes.
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影响因子：
7.7
作者：
Nejentsev, S;Gombos, Z;Ilonen, J
通讯作者：
Ilonen, J
DOI：
10.1073/pnas.0508621102
发表时间：
2005-12-20
影响因子：
11.1
作者：
Pinkse, GGM;Tysma, OHM;Roep, BO
通讯作者：
Roep, BO
影响因子：
8.2
作者：
FENNESSY, M;METCALFE, K;WETTENSTRAND, G
通讯作者：
WETTENSTRAND, G
影响因子：
5.7
作者：
HONEYMAN, MC;HARRISON, LC;TAIT, BD
通讯作者：
TAIT, BD
影响因子：
30.8
作者：
Clayton, DG;Walker, NM;Todd, JA
通讯作者：
Todd, JA