白细胞介素-10 基因多态性影响中国低三分位胃癌患者恶病质易感性。

Interleukin-10 gene polymorphisms influence susceptibility to cachexia in patients with low-third gastric cancer in a Chinese population.

机构信息

Department of General Surgery, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, China.

出版信息

Mol Diagn Ther. 2010 Apr 1;14(2):95-100. doi: 10.1007/BF03256358.

DOI:10.1007/BF03256358

PMID:20359252

Abstract

BACKGROUND AND OBJECTIVE

Interleukin (IL)-10 is a pleiotropic cytokine that can both stimulate and suppress the immune response. Previous studies have reported that IL-10 production was significantly elevated in cachectic patients, and it has been confirmed that polymorphisms of the IL10 gene could influence its expression. Therefore, we designed this study to investigate whether polymorphisms of the IL10 gene were associated with cachexia in patients with low-third gastric cancer in a Chinese population.

METHODS

190 patients with low-third gastric cancer were included in this study. The serum levels of IL-10 were measured by radioimmunoassay. The single nucleotide polymorphisms (SNPs) at positions -1082A/G, -819T/C, and -592A/C in the IL10 gene promoter were analyzed using polymerase chain reaction (PCR) restriction fragment length polymorphism (PCR-RFLP).

RESULTS

The serum levels of IL-10 were significantly higher in patients with cachexia than in those without (Z = -10.66, p < 0.001). Single SNP analysis showed that the frequency of the IL10 -1082G allele was increased in patients with cachexia (p = 0.02). The -1082AG and -819CC genotypes were observed to be associated with an increased risk of cachexia. In a logistic regression analysis adjusted for actual weight and carcinoma stage, the -1082AG genotype was associated with an odds ratio (OR) of 2.45 (95% CI 1.21, 4.96; p = 0.01), and the -819CC genotype was associated with an OR of 3.70 (95% CI 1.20, 11.39; p = 0.02) for cachexia. Furthermore, haplotype analysis of the -1082A/G, -819T/C, and -592A/C SNPs revealed that at least five haplotypes (ATA, ACC, GCC, ACA, and ATC) were present in this Chinese population, and the -1082G/-819C/-592C (GCC) haplotype was associated with a significantly increased risk of cachexia as compared with the ATA haplotype (OR = 2.42; 95% CI 1.17, 5.00; p = 0.02).

CONCLUSION

Our results indicate that genetic polymorphisms of IL-10 may influence susceptibility to cachexia in patients with low-third gastric cancer in this Chinese population.

摘要

背景与目的

白细胞介素（IL）-10 是一种具有多种功能的细胞因子，既能刺激又能抑制免疫反应。先前的研究报道，恶病质患者的 IL-10 产生显著升高，并且已经证实 IL10 基因的多态性可能影响其表达。因此，我们设计了这项研究，以探讨中国人群低三分位胃癌患者 IL10 基因多态性是否与恶病质有关。

方法

本研究纳入了 190 例低三分位胃癌患者。采用放射免疫法检测血清 IL-10 水平。采用聚合酶链反应（PCR）限制性片段长度多态性（PCR-RFLP）分析 IL10 基因启动子 -1082A/G、-819T/C 和 -592A/C 处的单核苷酸多态性（SNP）。

结果

恶病质患者的血清 IL-10 水平明显高于无恶病质患者（Z = -10.66，p < 0.001）。单 SNP 分析显示，恶病质患者的 IL10-1082G 等位基因频率增加（p = 0.02）。-1082AG 和 -819CC 基因型与恶病质的发生风险增加相关。在调整实际体重和癌肿分期的 logistic 回归分析中，-1082AG 基因型与 2.45 倍的比值比（OR）相关（95%CI 1.21，4.96；p = 0.01），-819CC 基因型与 3.70 倍的 OR 相关（95%CI 1.20，11.39；p = 0.02）。此外，-1082A/G、-819T/C 和 -592A/C SNP 的单体型分析显示，在中国人群中至少存在 5 种单体型（ATA、ACC、GCC、ACA 和 ATC），-1082G/-819C/-592C（GCC）单体型与 ATA 单体型相比，恶病质的发生风险显著增加（OR = 2.42；95%CI 1.17，5.00；p = 0.02）。