Common variants in genes that mediate immunity and risk of multiple myeloma
Common variants in genes that mediate immunity and risk of multiple myeloma
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DOI：
10.1002/ijc.22618
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发表时间：
2007-06-15
影响因子：
6.4
通讯作者：
Baris, Dalsu
中科院分区：
文献类型：
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作者：
Brown, Elizabeth E.;Lan, Qing;Baris, Dalsu
多发性骨髓瘤（MM）是一种以免疫功能异常为特征的B细胞恶性肿瘤。使用从127例年龄在21-84岁之间的MM病例和545例基于人群的对照中提取的基因组DNA，我们研究了与45个基因中的82个常见变异相关的MM风险，这些基因介导了欧洲裔美国女性的免疫力。使用经验证和优化的TaqMan测定法确定基因分型。我们估计单倍型频率从非定相的基因型数据为20个这些基因使用期望最大化渐进插入算法。与对照组相比，MM风险与IL 4 R（-28120T，rs 2107356）和FCGR 2A（-120G，rs 1801274）单基因座纯合子正相关（OR分别为1.91，95%CI 1.08-3.38和1-95，95%CI 1.06-3.60）。对于在多个位点之间观察到连锁不平衡的基因，MM风险与单倍型块覆盖正相关，LTA*TNF复合物的一部分（LTA-82 C/-90 G *TNF-1036 C/-487 G/-417 G，OR = 1.63，95%CI 1.02-2.16）与对照组中观察到的最常见单倍型（LTA-82 A/-90 A *TNF-1036 C/-487 G./- 417 G）。我们的研究结果提供了初步证据，表明特定免疫介导途径中的常见遗传变异可能影响MM的风险。
Multiple myeloma (MM) is a B-cell malignancy characterized by aberrant immune function. Using genomic DNA extracted from 127 MM cases aged 21-84 years and 545 population-based controls, we examined the risks of MM associated with 82 common variants in 45 genes that mediate immunity among women of European American descent. Genotyping was determined using validated and optimized TaqMan assays. We estimated haplotype frequencies from unphased genotype data for 20 of these genes using the expectation-maximization progressive insertion algorithm. Compared with controls, MM risk was positively associated with homozygotes of single loci, IL4R (-28120T, rs2107356) and FCGR2A (-120G, rs1801274) (OR = 1.91, 95% CI 1.08-3.38 and 1-95, 95% CI 1.06-3.60, respectively). For genes in which linkage disequilibrium was observed between multiple loci, MM risk was positively associated with the haplotype block covering, part of the LTA*TNF complex (LTA -82C/-90G *TNF -1036C/-487G/ -417G, OR = 1.63, 95% CI 1.02-2.16) compared with the most frequently occurring haplotype observed among controls (LTA -82A/-90A *TNF -1036C/-487G./-417G). Our findings provide preliminary evidence that common genetic variants in specific immune-mediaied pathways could influence the risk of MM. (c) 2007 Wiley-Liss, Inc.