Banu C, Moise A, Arion C V, Coriu D, Tănase A, Constantinescu I
National Institute for Medical Assessment and Work Capacity Rehabilitation, Bucharest, Romania.
J Med Life. 2011 Aug 15;4(3):264-8. Epub 2011 Aug 25.
Cytokines and their receptor genes are very polymorphic. SNPs in the promotor region of the gene may influence the rate of cytokine secretion and may affect the biological activity of the encoded cytokine. A number of cytokines and cytokine receptors have been directly linked to the development of human cancers. The aim of our study was to determine the cytokine gene polymorphism in Romanian multiple myeloma patients.
Cytokine genotyping was performed in 80 patients and 100 healthy blood donors using molecular biology methods (SSP-Invitrogen, USA).
Analyzing each polymorphic site, there was an increased frequency of the following genotypes in patients compared to control group: Interleukin-1beta (IL-1β) pos.+3962 TT, IL-12 pos.-1188 CC, gamma-Interferon (γ-IFN) pos.+874 AA, Transforming Growth Factor- beta1 (TGF- β1) codon10 TT, IL-2 pos.-330 TG and pos.+166 TT, Interleukin-4Receptor alpha (IL-4Rα) pos.-33 TC, IL-10 pos.-1082 GG and pos.-592 CC, IL-6 pos.-174 GG. It should be noted that almost one third of multiple myeloma patients had IL-6 pos.-174 GG genotype and 62% IL-10 GCC haplotype. These identified haplotypes are high interleukins producer, and this fact was confirmed by serum IL-6 and IL-10 levels performed by ELISA and enhanced chemiluminiscence methods.
These markers could be successfully used, together with other specific clinical and biological parameters, as reliable individualized prognostic factors in multiple myeloma patients.
细胞因子及其受体基因具有高度多态性。基因启动子区域的单核苷酸多态性(SNP)可能会影响细胞因子的分泌速率,并可能影响所编码细胞因子的生物学活性。许多细胞因子和细胞因子受体已被直接与人类癌症的发生发展联系起来。我们研究的目的是确定罗马尼亚多发性骨髓瘤患者的细胞因子基因多态性。
采用分子生物学方法(美国赛默飞世尔科技公司的序列特异性引物法)对80例患者和100名健康献血者进行细胞因子基因分型。
分析每个多态性位点,与对照组相比,患者中以下基因型的频率增加:白细胞介素-1β(IL-1β)+3962位TT、白细胞介素-12 -1188位CC、γ-干扰素(γ-IFN)+874位AA、转化生长因子-β1(TGF-β1)第10密码子TT、白细胞介素-2 -330位TG和+166位TT、白细胞介素-4受体α(IL-4Rα)-33位TC;白细胞介素-10 -1082位GG和-592位CC、白细胞介素-6 -174位GG。应当指出的是,几乎三分之一的多发性骨髓瘤患者具有白细胞介素-6 -174位GG基因型,62%的患者具有白细胞介素-10 GCC单倍型。这些鉴定出的单倍型是高白细胞介素产生者,这一事实通过酶联免疫吸附测定(ELISA)和增强化学发光法检测的血清白细胞介素-6和白细胞介素-10水平得到了证实。
这些标志物可与其他特定的临床和生物学参数一起成功用作多发性骨髓瘤患者可靠的个体化预后因素。