白介素-23受体基因多态性与乙肝相关肝细胞癌的易感性研究

Association between Interleukin-23R Gene Polymorphisms and Susceptibility to Hepatitis B-related Hepatocellular Carcinoma

目的:探讨白介素-23受体(IL-23R)基因多态性与广西壮族人群乙肝相关肝细胞癌(HCC)易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对84例乙肝表面抗原(HBSAg)阳性HCC患者(病例组)和94例HbsAg阳性体检者(对照组)IL-23R基因rs10889677、rs1884444、rs114658173个位点的单核苷酸多态性进行检测及其部分标本进行直接测序鉴定。采用SHEsis软件构建IL-23R基因3个位点的单体型。Logistic回归分析IL-23R基因多态性和单体型与HCC遗传易感性的关系。结果:IL-23Rrs10889677、rs11465817位点的AA、AC、CC3种基因型和A、C两种等位基因在HCC组与对照组之间的分布差异无统计学意义(P>0.05)。rs1884444位点的TT、TG、GG三种基因型及T、G两种等位基因在病例组和对照组的频率分布差异均有统计学意义(P均<0.05),Logistic回归分析发现携带TG基因型的个体发生HCC的风险较携带TT基因型的个体增加(校正OR=2.20,95%CI=1.11～4.37)。单体型构建发现CGC、AGC、CTC、ATC、CGA、AGA、CTA、ATA等8种单倍体,病例组和对照组的AGC单倍体分布差异有统计学意义(P<0.05),AGC单倍体携带者发生HCC的风险明显增加(校正OR=2.71,95%CI=1.06～6.93)。结论:IL-23R基因rs1884444位点TG基因型可能是HCC发病的危险因子;乙肝背景下AGC单倍体携带者患HCC的风险增加2.71倍,可能是乙肝相关肝癌发病的危险因素。

Objective: To investigate the association between interleukin-23R (IL-23R) gene polymorphisms and susceptibility to hepatitis B-related hepatocellular carcinoma (HCC) in guangxi zhuang population. Method: 84 cases of patient with HBV-related HCC and 94 cases of HbsAg positive cancer-free controls were included in this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotypes of IL-23R rs10889677, rs1884444, rs11465817 polymorphisms and direct sequencing was conducted to identify genotyping results. The haplotypes were constructed using SHEsis software. Results: With respect to genotypes and alleles distribution of the IL-23R gene rs10889677, rs11465817 polymorphisms, there were no significant differences between the two groups. However, significant differences in the distribution of the genotypes and alleles were observed in rs1884444 polymorphism between the HCC group and the control group (P=0.033 and P=0.037, respectively). The carriers of rs1884444 TG genotype were associated with increased HCC risk as compared with the subjects with TT genotype in Logistic analysis (adjusted OR=2.20, 95%CI=1.11~4.37). There were 8 haplotypes in haplotype construction analysis, increased HCC risk was found among the individuals carrying AGC haplotype (adjusted OR=2.71, 95%CI=1.06~6.93). Conclusion: The TG genotype of IL-23R rs1884444 polymorphism may be a risk factor for hepatitis B-related HCC. The AGC haplotype of IL-23R rs10889677, rs1884444, rs11465817 polymorphisms was associated with 2.71 times of increased HCC risk, the AGC haplotype is a risk factor for hepatitis B-related HCC.