Department of Statistics, University of Oxford, Oxford, United Kingdom.
Blood. 2011 Jul 21;118(3):670-4. doi: 10.1182/blood-2011-03-339630. Epub 2011 May 19.
Since an association between the human leukocyte antigen (HLA) region and Hodgkin lymphoma (HL) was first reported in 1967, many studies have reported associations between HL risk and both single nucleotide polymorphism (SNP) and classic HLA allele variation in the major histocompatibility complex. However, population stratification and the extent and complexity of linkage disequilibrium within the major histocompatibility complex have hindered efforts to fine-map causal signals. Using SNP data to impute alleles at classic HLA loci, we have conducted an integrated analysis of HL risk within the HLA region in 582 early-onset HL cases and 4736 controls. We confirm that the strongest signal of association comes from an SNP located in the class II region, rs6903608 (odds ratio [OR] = 1.79, P = 6.63 × 10(-19)), which is unlikely to be driven by association to HLA-DRB, DQA, or DQB alleles. In addition, we identify independent signals at rs2281389 (OR = 1.73, P = 6.31 × 10(-13)), a SNP that maps closely to HLA-DPB1, and the class II HLA allele DQA1*02:01 (OR = 0.56, P = 1.51 × 10(-7)). These data suggest that multiple independent loci within the HLA class II region contribute to the risk of developing early-onset HL.
自 1967 年首次报道人类白细胞抗原 (HLA) 区域与霍奇金淋巴瘤 (HL) 之间存在关联以来，许多研究报告了 HL 风险与主要组织相容性复合体中单核苷酸多态性 (SNP) 和经典 HLA 等位基因变异之间的关联。然而，人群分层以及主要组织相容性复合体内部的连锁不平衡的程度和复杂性阻碍了精细映射因果信号的努力。我们使用 SNP 数据推断经典 HLA 基因座上的等位基因，对 582 例早发性 HL 病例和 4736 例对照者 HLA 区域内的 HL 风险进行了综合分析。我们证实，最强的关联信号来自位于 II 类区域的 SNP rs6903608（比值比 [OR] = 1.79，P = 6.63×10(-19)），该 SNP 不太可能是与 HLA-DRB、DQA 或 DQB 等位基因关联驱动的。此外，我们还确定了位于 rs2281389（OR = 1.73，P = 6.31×10(-13)）和 HLA-DPB1 紧密映射的 SNP 以及 II 类 HLA 等位基因 DQA1*02:01（OR = 0.56，P = 1.51×10(-7)）的独立信号。这些数据表明，HLA Ⅱ类区域内的多个独立位点与早发性 HL 的发病风险相关。
