Vangsted A J, Klausen T W, Ruminski W, Gimsing P, Andersen N F, Gang A O, Abildgaard N, Knudsen L M, Nielsen J L, Gregersen H, Vogel U
Department of Oncology and Hematology, Roskilde County Hospital, Roskilde, Denmark.
Bone Marrow Transplant. 2009 Apr;43(7):539-45. doi: 10.1038/bmt.2008.351. Epub 2008 Nov 10.
Proinflammatory cytokines are suspected to play a role in the pathogenesis of multiple myeloma (MM). Therefore, it is possible that inborn genetic variations leading to a modified expression of these cytokines will influence the outcome for these patients. We investigated 348 MM patients undergoing high-dose melphalan treatment followed by Auto-SCT and examined the influence of single nucleotide polymorphisms (SNPs) in genes involved in the inflammatory response. We found that the polymorphism IL-1beta T-31C significantly influenced overall survival (OS; P=0.02) and that carriers of the variant C-allele had a significantly longer survival than homozygous wild-type allele TT-carriers (relative risk 0.6 (95% CI=0.5-0.9); P=0.008). The polymorphisms IL-6 G-174C, IL-10 C592A, PPARgamma2 Pro(12)Ala, COX-2 A-1195G, COX-2 T8473C and NFKB1 ins/del did not influence the OS in this group of patients. Furthermore, homozygous carriers of the variant allele of IL-1beta T-31C were at 1.37-fold (CI=1.05-1.80) increased risk of MM as compared with population-based controls (P=0.02). Our results indicate that IL-1beta is involved in the pathogenesis of MM.
促炎细胞因子被怀疑在多发性骨髓瘤（MM）的发病机制中起作用。因此，导致这些细胞因子表达改变的先天性基因变异可能会影响这些患者的预后。我们调查了348例接受大剂量美法仑治疗后进行自体造血干细胞移植（Auto-SCT）的MM患者，并研究了参与炎症反应的基因中的单核苷酸多态性（SNP）的影响。我们发现，白细胞介素-1β（IL-1β）基因T-31C多态性显著影响总生存期（OS；P=0.02），携带变异C等位基因的患者生存期明显长于纯合野生型等位基因TT携带者（相对风险0.6（95%CI=0.5-0.9）；P=0.008）。白细胞介素-6（IL-6）基因G-174C、白细胞介素-10（IL-10）基因C592A、过氧化物酶体增殖物激活受体γ2（PPARγ2）基因Pro(12)Ala、环氧化酶-2（COX-2）基因A-1195G、COX-2基因T8473C和核因子κB1（NFKB1）基因插入/缺失多态性在该组患者中未影响总生存期。此外，与基于人群的对照组相比，IL-1β基因T-31C变异等位基因的纯合携带者患MM的风险增加了1.37倍（CI=1.05-1.80）（P=0.02）。我们的结果表明，IL-1β参与了MM的发病机制。
