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白细胞介素-16 遗传多态性影响中国人群乙型肝炎病毒相关肝细胞癌的易感性。

Genetic polymorphism of interleukin-16 influences susceptibility to HBV-related hepatocellular carcinoma in a Chinese population.

机构信息

Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.

出版信息

Infect Genet Evol. 2011 Dec;11(8):2083-8. doi: 10.1016/j.meegid.2011.09.025. Epub 2011 Oct 12.

DOI:10.1016/j.meegid.2011.09.025
PMID:22019522
Abstract

AIM

Interleukin-16 (IL16) as a multifunctional cytokine, plays a key role in inflammatory and autoimmune diseases as well as tumour growth and progression. Recently, genetic polymorphisms of IL16 have been reported to be associated with susceptibility to a range of cancers. This study was undertaken to investigate the IL16 gene polymorphisms and determine whether these genetic factors are related to the occurrence of hepatocellular carcinoma (HCC) in a Chinese population.

METHODS

We analyzed three polymorphisms of the IL16 gene (rs11556218T/G, rs4072111C/T and rs4778889T/C) in 206 patients with HBV-related HCC, 270 chronic hepatitis B patients and 264 healthy controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and DNA sequencing technology.

RESULTS

IL16 polymorphisms were not associated with risk of HCC when compared with healthy controls. However, IL16 polymorphisms were significantly associated with susceptibility to HBV-related HCC when using chronic hepatitis B patients as controls. The rs11556218T/G TG and GG genotypes were associated with significantly increased risk of HBV-related HCC compared with the TT genotype (OR = 1.96 and OR = 3.33). The data also revealed that subjects with the G allele appeared to have higher susceptibility to HBV-related HCC than those with the T allele (OR = 2.10). Under the dominant model genotype TG+GG appeared to be associated with an increased risk of HBV-related HCC (OR = 2.18). The rs4072111C/T TT genotype was associated with a significantly increased risk of HBV-related HCC compared with the CC genotype (OR = 6.67). Polymorphisms of the IL16 gene were significantly associated with susceptibility to chronic hepatitis B when using healthy subjects as controls. The rs11556218T/G TG and GG genotypes were associated with significantly decreased risk of chronic hepatitis B compared with the TT genotype (OR = 0.49 and OR = 0.29). The data also revealed that subjects with the G allele appeared to have lower susceptibility to chronic hepatitis B than those with the T allele (OR = 0.46). Under the dominant model genotype TG + GG appeared to have lower susceptibility to chronic hepatitis B (OR = 0.44).

CONCLUSIONS

This study showed that the genotypes and allele of IL16 SNPs were associated with chronic HBV infection and HCC. However, further investigation with a larger sample size and haplotype analysis with other SNPs may be required to validate the genetic effects of the IL16 polymorphisms on chronic HBV infection and HCC.

摘要

目的

白细胞介素 16(IL16)作为一种多功能细胞因子,在炎症和自身免疫性疾病以及肿瘤生长和进展中发挥关键作用。最近,IL16 的基因多态性已被报道与多种癌症的易感性有关。本研究旨在探讨 IL16 基因多态性,确定这些遗传因素是否与中国人群肝细胞癌(HCC)的发生有关。

方法

采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法和 DNA 测序技术,分析 206 例乙型肝炎病毒(HBV)相关 HCC 患者、270 例慢性乙型肝炎患者和 264 例健康对照者的 IL16 基因三个多态性(rs11556218T/G、rs4072111C/T 和 rs4778889T/C)。

结果

与健康对照组相比,IL16 多态性与 HCC 风险无相关性。然而,当以慢性乙型肝炎患者为对照时,IL16 多态性与 HBV 相关 HCC 的易感性显著相关。与 TT 基因型相比,rs11556218T/G 的 TG 和 GG 基因型与 HBV 相关 HCC 的风险显著增加(OR=1.96 和 OR=3.33)。数据还显示,与 T 等位基因相比,G 等位基因的个体似乎更容易发生 HBV 相关 HCC(OR=2.10)。在显性模型中,TG+GG 基因型似乎与 HBV 相关 HCC 的风险增加相关(OR=2.18)。与 CC 基因型相比,rs4072111C/T 的 TT 基因型与 HBV 相关 HCC 的风险显著增加(OR=6.67)。当以健康受试者为对照时,IL16 基因多态性与慢性乙型肝炎的易感性显著相关。与 TT 基因型相比,rs11556218T/G 的 TG 和 GG 基因型与慢性乙型肝炎的风险显著降低(OR=0.49 和 OR=0.29)。数据还显示,与 T 等位基因相比,G 等位基因的个体似乎更容易发生慢性乙型肝炎(OR=0.46)。在显性模型中,TG+GG 基因型似乎对慢性乙型肝炎的易感性降低(OR=0.44)。

结论

本研究表明,IL16 SNP 的基因型和等位基因与慢性 HBV 感染和 HCC 相关。然而,需要进一步进行更大样本量的研究和其他 SNP 的单体型分析,以验证 IL16 多态性对慢性 HBV 感染和 HCC 的遗传影响。

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