Serum Interleukin-6 Level and the rs1800795 Polymorphism in its Gene Associated with Neuroblastoma Risk in Chinese Children

: 外周血白细胞介素-6水平及其rs1800795位点基因单核苷酸多态性与儿童神经母细胞瘤的相关性研究摘要目的：白细胞介素-6（IL-6）是一种促炎性细胞因子，对肿瘤的转移有促进作用。有研究显示IL-6及其单核苷酸多态性(single nucleotide polymorphisms, SNP) rs1800795与美国和意大利的人群中的神经母细胞瘤（NB）有关。本文主要探讨外周血IL-6水平及其rs1800795位点SNP与中国NB儿童之间的相关性。 方法：收集我院诊治的NB患儿共130例，分为两组(中低危组及高危组)，及同期年龄和性别匹配的健康儿童50例作为对照组，应用PCR和基因测序的方法，分析L-6水平及其rs1800795位点的SNP与儿童NB的危险度和预后之间的关系。 结果：NB组共有男孩77例(59%)和女孩53例(41%)，平均年龄41±5个月，其中高危组患儿87例，中低危组患儿43例。Rs1800795位点的各基因型及等位基因，在NB患儿及正常儿童中的分布均无明显差异（P>0.05）；在高危组患儿中GG + GC基因型频率高于非高危患儿 (64.4% vs. 48.8%, P = 0.02)，而高危患儿中，伴GG + GC基因型的血清IL-6水平比CC基因型高 (4.36 ± 1.1 pg/ml vs. 1.83 ± 0.5 pg/ml; P = 0.02)，但非高危患儿无此现象。 结论：外周血IL-6水平及rs1800795位点的基因多态性与NB的危险度及预后相关。GG基因型可能提示肿瘤高度恶性，易转移，预后差。. Methods: A total of 130 NB patients, with 77 boys (59%), 53 girls (41%), mean age 41 ± 5 months, were assigned to two groups: high risk (HR) versus intermediate-low risk (non-HR), and 50 healthy children were randomly selected as the age- and gender-matched controls. Peripheral blood samples were analyzed to determine serum IL-6 level using enzyme linked immunosorbent assay and rs1800795 SNPs phenotype using polymerase chain reaction and gene sequencing. Results: There were 87 NB patients in the HR group and 43 NB patients in the non-HR group. A comparison of allele and genotype frequencies of the rs1800795 polymorphism between patients and controls found no association with NB risk (P > 0.05). The frequency of GG+GC genotype was higher in HR-NB patients than in non-HR-NB patients (64.4% vs. 48.8%, P = 0.02), and serum IL-6 level was much higher in HR-NB patients with GG+GC genotype than in HR-NB patients with CC genotype (4.36 ± 1.1 pg/ml vs. 1.83 ± 0.5 pg/ml; P = 0.02), but not in Non-HR-NB patients. Conclusions: The polymorphism rs1800795 is associated with serum IL-6 level and level of NB risk. GG genotype might indicate that the tumor is highly malignant (prone to metastasis) and associated with poor prognosis.