A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32
A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32
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DOI：
10.1182/blood-2011-03-343921
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发表时间：
2012-01-12
期刊：
影响因子：
20.3
通讯作者：
Onel, Kenan
中科院分区：
文献类型：
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作者：
Cozen, Wendy;Li, Dalin;Onel, Kenan
结节硬化性霍奇金淋巴瘤（NSHL）是一种独特的，高度遗传性霍奇金淋巴瘤亚型。我们使用Illumina Human 610-Quad Beadchip和Affyssin全基因组人类SNP阵列6.0对393名欧洲青少年/年轻成人NSHL患者和3315名对照进行了全基因组荟萃分析。我们在染色体6p21.32上发现了3个与NSHL风险显著相关的单核苷酸多态性（SNP）：rs 9268542（P = 5.35 x 10（-10）），rs 204999（P = 1.44 x 10（-9））和rs 2858870（P = 1.69 x 10（-8））。我们还证实了先前报道的同一区域rs6903608的相关性（P = 3.52 x 10（-10））。rs 204999和rs 2858870弱相关（r（2）= 0.257），其余SNP对不相关（r（2）< 0.1）。在113例NSHL病例和214例对照的独立组中，2个SNP与NSHL显著相关，第三个SNP显示出相当的比值比（OR）。这些SNP存在于与NSHL风险相关的2种单倍型上（rs 204999-rs 9268528-rs 9268542-rs6903608-rs 2858870; AGGCT，OR = 1.7，P = 1.71 x 10（-6）; GAATC，OR = 0.4，P = 1.16 x 10（-4））。所有具有GAATC单倍型的个体也携带HLA II类DRB 1 *0701等位基因。在一项单独的分析中，DRB 1 *0701等位基因与NSHL风险降低相关（OR = 0.5，95%置信区间= 0.4，0.7）。这些数据支持HLA II类区域在NSHL病因学中的重要性。（血。2012;119（2）：469-475）
Nodular sclerosing Hodgkin lymphoma (NSHL) is a distinct, highly heritable Hodgkin lymphoma subtype. We undertook a genome-wide meta-analysis of 393 European-origin adolescent/young adult NSHL patients and 3315 controls using the Illumina Human610-Quad Beadchip and Affymetrix Genome-Wide Human SNP Array 6.0. We identified 3 single nucleotide polymorphisms (SNPs) on chromosome 6p21.32 that were significantly associated with NSHL risk: rs9268542 (P = 5.35 x 10(-10)), rs204999 (P = 1.44 x 10(-9)), and rs2858870 (P = 1.69 x 10(-8)). We also confirmed a previously reported association in the same region, rs6903608 (P = 3.52 x 10(-10)). rs204999 and rs2858870 were weakly correlated (r(2) = 0.257), and the remaining pairs of SNPs were not correlated (r(2) < 0.1). In an independent set of 113 NSHL cases and 214 controls, 2 SNPs were significantly associated with NSHL and a third showed a comparable odds ratio (OR). These SNPs are found on 2 haplotypes associated with NSHL risk (rs204999-rs9268528-rs9268542-rs6903608-rs2858870; AGGCT, OR = 1.7, P = 1.71 x 10(-6); GAATC, OR = 0.4, P = 1.16 x 10(-4)). All individuals with the GAATC haplotype also carried the HLA class II DRB1*0701 allele. In a separate analysis, the DRB1*0701 allele was associated with a decreased risk of NSHL (OR = 0.5, 95% confidence interval = 0.4, 0.7). These data support the importance of the HLA class II region in NSHL etiology. (Blood. 2012;119(2):469-475)