白介素-16基因多态性与肝癌遗传易感性研究
摘要
目的:研究白介素-16(IL-16)基因rs11556218T/G、rs4072111C/T、rs4778889T/C三个位点的多态性,希望通过此项群体研究,在广西人群中揭示IL-16的基因多态性与肝癌的遗传相关性,获得具有重要功能意义的与肝癌遗传易感性相关的SNP或单倍型,为肝癌的人群预防提供新的遗传标记以及为肝癌的治疗提供新靶标。
方法:对来自肝癌高发区广西的141例肝癌患者(肝癌组)和142例健康体检者(对照组),采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法及DNA测序法,分别检测IL-16基因rs11556218T/G、rs4072111C/T、rs4778889T/C三个位点的多态性,用χ~2检验比较基因型和等位基因在肝癌组和对照组间的差异,logstic回归分析计算比值比(Oddsratios,OR)和95%可信区间(Confidence Intervals,CI),并以性别和年龄进行校正,对基因多态性和肝癌的易感性进行关联分析。以上统计均采用SPSS 13.0软件。采用PLINK软件构建单倍型并进行分析。
结果:
1.肝癌组和对照组在性别和年龄组成上的差异无统计学意义(P>0.05),具有可比性。肝癌组和对照组IL-16 rs11556218T/G、rs4072111C/T、rs4778889T/C三个位点基因型均符合Hardy-weinberg平衡,所检测的样本具有代表性和可比性。2. IL-16 rs11556218T/G位点共有TT、TG、GG三种基因型,三个基因型在肝癌组和对照组中分布频率的差异无统计学意义(P=0.97)。与TT基因型相比,TG基因型和肝癌的患病风险无相关性(P=0.38), GG基因型和肝癌的患病风险无相关性(P=0.90),说明IL-16 rs11556218T/G位点的基因多态性与肝癌的遗传易感性无关。
3. IL-16 rs4072111C/T位点共有CC、CT、TT三种基因型,三个基因型在肝癌组和对照组中分布频率的差异无统计学意义(P=0.59)。与CC基因型相比,CT基因型和肝癌的患病风险无相关性(P=0.46),TT基因型和肝癌的患病风险无相关性(P=0.64),说明IL-16 rs4072111C/T位点的基因多态性与肝癌的遗传易感性无关。
4. IL-16 rs4778889T/C位点共有TT、TC、CC三种基因型,三个基因型在肝癌组和对照组中分布频率的差异无统计学意义(P=0.12)。与TT基因型相比,TC基因型和肝癌的患病风险有相关性(P=0.04),CC基因型和肝癌的患病风险无相关性(P=0.59)。与TT基因型相比,TC基因型患肝癌的风险显著降低至0.50倍,说明TC基因型有可能是肝癌的一个保护因素。
5. IL-16三个SNP的频率在对照组中的分布与华西地区、北京和日本等地研究的结果较类似,与美国犹他州、尼日利亚人群等研究的结果差异较大。
6.无论是在男性人群中还是在女性人群中,IL-16 rs11556218T/G、rs4072111C/T、rs4778889T/C三个位点的基因型与肝癌的患病风险无相关性(P>0.05)。
7.无论是在HBV携带人群中还是在非HBV携带人群中,IL-16 rs11556218T/G、rs4072111C/T、rs4778889T/C三个位点的基因型与肝癌的患病风险无相关性(P>0.05)。
8. GTC单倍型在肝癌组中的频率显著低于在对照组中的频率,GTC单倍型患肝癌的风险显著减低至0.02(P=0.03),提示GTC单倍型有可能是肝癌的一个保护因素。其他单倍型与肝癌的患病风险无相关性(P>0.05)。
结论:IL-16 rs4778889T/C位点TC基因型与肝癌的遗传易感性相关,TC基因型患肝癌的风险显著降低至0.50倍,说明TC基因型有可能是肝癌的一个保护因素。IL-16三个SNP的频率在对照组中的分布与华西地区、北京和日本等地研究的结果较类似,与美国犹他州、尼日利亚人群等研究的结果差异较大。GTC单倍型患肝癌的风险显著减低至0.02,提示GTC单倍型有可能是肝癌的一个保护因素。
Objectives To study polymorphisms between rs11556218T / G, rs4778889T/C and rs4072111C/T of interleukin -16 (IL-16) gene. To reveal the association between polymorphisms of IL-16 and hepatocellular carcinoma in GuangXi population. To obtain the important SNP or haplotype which was associated with the susceptibility to hepatocellular carcinoma, providing new genetic markers for the prevention of hepatocellular carcinoma and new target for the treatment of hepatocellular carcinoma.
Methods Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) strategy and DNA sequencing methods were used to analyze polymorphisms of IL-16 in 141 patients with HCC and age, sex-matched 142 healthy controls. Usingχ~2 test to exam the differences of genotype, allele, haplotype between the HCC group and control group, logstic regression was used to analysis odds ratio (Oddsratios, OR) and 95% CI(Confidence Intervals, CI), adjusted for sex and age by the logistic regression model, analysis the association between SNPs of polymorphisms and hepatocellular carcinoma. All the results were analyzed by SPSS 13.0. Using PLINK software to construct the haplotypes and analyzed.
Results
1. The differences of gender and age composition between HCC group and control group were not statistically significant(P>0.05). Genotype of IL-16 rs11556218T / G, rs4072111C / T, rs4778889T / C in HCC group and control group were consistent with Hardy-weinberg equilibrium, the samples detected were representative and comparable.
2. There were TT, TG and GG three genotypes in IL-16 rs11556218T / G, the difference of the frequency distribution between the two groups was no statistically significant (P =0.97). Comparing with TT genotype, TG genotype was not associated with susceptibility to hepatocellular carcinoma (P = 0.38), GG genotype was not associated with susceptibility to hepatocellular carcinoma (P =0.90). The genetic polymorphism of IL-16 rs11556218T / G was not associated with susceptibility to hepatocellular carcinoma.
3. There were CC, CT and TT three genotypes in IL-16 rs4072111C/T, the difference of the frequency distribution between the two groups was no statistically significant (P = 0.59). Comparing with CC genotype, CT genotype was not associated with susceptibility to hepatocellular carcinoma (P = 0.46), TT genotype was not associated with susceptibility to hepatocellular carcinoma (P =0.64). The genetic polymorphism of IL-16 rs4072111C/T was not associated with susceptibility to hepatocellular carcinoma.
4. There were TT, TC and CC three genotypes in IL-16 rs4778889T / C, the difference of the frequency distribution between the two groups was no statistically significant (P = 0.12). Comparing with TT genotype, TC genotype was associated with susceptibility to hepatocellular carcinoma(P=0.04), CC genotype was no associated with susceptibility to hepatocellular carcinoma (P =0.59). Comparing with TT genotype, the risk of patients carrying TC genotype developing hepatocellular carcinoma was significantly reduced to 0.5. The TC genotype maybe a protective factor for hepatocellular carcinoma.
5. The distribution of the three SNPs in the control group were similar to the findings from the west regions of China, Beijing and Japan, but there were differences when compared with the Utah of United States and Nigeria.
6. Both in the male and female population, the three SNPs of IL-16 were not associated with susceptibility to hepatocellular carcinoma (P>0.05).
7. Both in HBV carriers and non-HBV carrier population, the three SNPs of IL-16 were not associated with susceptibility to hepatocellular carcinoma (P>0.05).
8. The GTC haplotype frequency in the HCC group was significantly lower than that in the control group. The risk of patients carrying the GTC developing hepatocellular carcinoma was significantly reduced to 0.02. The GTC haplotype maybe a protective factor for hepatocellular carcinoma. The other haplotypes were not associated with susceptibility to hepatocellular carcinoma (P>0.05).
Conclution The rs4778889T/C polymorphism of TC genotype was significantly associated with the susceptibility to HCC. The risk of patients carrying TC genotype developing hepatocellular carcinoma was significantly reduced to 0.5. The TC genotype maybe a protective factor for hepatocellular carcinoma. The distribution of the three SNPs in the control group were similar to the findings from the west regions of China, Beijing and Japan, but there were differences when compared with the Utah of United States and Nigeria. The risk of patients carrying the GTC developing hepatocellular carcinoma was significantly reduced to 0.02. The GTC haplotype maybe a protective factor for hepatocellular carcinoma.
方法:对来自肝癌高发区广西的141例肝癌患者(肝癌组)和142例健康体检者(对照组),采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法及DNA测序法,分别检测IL-16基因rs11556218T/G、rs4072111C/T、rs4778889T/C三个位点的多态性,用χ~2检验比较基因型和等位基因在肝癌组和对照组间的差异,logstic回归分析计算比值比(Oddsratios,OR)和95%可信区间(Confidence Intervals,CI),并以性别和年龄进行校正,对基因多态性和肝癌的易感性进行关联分析。以上统计均采用SPSS 13.0软件。采用PLINK软件构建单倍型并进行分析。
结果:
1.肝癌组和对照组在性别和年龄组成上的差异无统计学意义(P>0.05),具有可比性。肝癌组和对照组IL-16 rs11556218T/G、rs4072111C/T、rs4778889T/C三个位点基因型均符合Hardy-weinberg平衡,所检测的样本具有代表性和可比性。2. IL-16 rs11556218T/G位点共有TT、TG、GG三种基因型,三个基因型在肝癌组和对照组中分布频率的差异无统计学意义(P=0.97)。与TT基因型相比,TG基因型和肝癌的患病风险无相关性(P=0.38), GG基因型和肝癌的患病风险无相关性(P=0.90),说明IL-16 rs11556218T/G位点的基因多态性与肝癌的遗传易感性无关。
3. IL-16 rs4072111C/T位点共有CC、CT、TT三种基因型,三个基因型在肝癌组和对照组中分布频率的差异无统计学意义(P=0.59)。与CC基因型相比,CT基因型和肝癌的患病风险无相关性(P=0.46),TT基因型和肝癌的患病风险无相关性(P=0.64),说明IL-16 rs4072111C/T位点的基因多态性与肝癌的遗传易感性无关。
4. IL-16 rs4778889T/C位点共有TT、TC、CC三种基因型,三个基因型在肝癌组和对照组中分布频率的差异无统计学意义(P=0.12)。与TT基因型相比,TC基因型和肝癌的患病风险有相关性(P=0.04),CC基因型和肝癌的患病风险无相关性(P=0.59)。与TT基因型相比,TC基因型患肝癌的风险显著降低至0.50倍,说明TC基因型有可能是肝癌的一个保护因素。
5. IL-16三个SNP的频率在对照组中的分布与华西地区、北京和日本等地研究的结果较类似,与美国犹他州、尼日利亚人群等研究的结果差异较大。
6.无论是在男性人群中还是在女性人群中,IL-16 rs11556218T/G、rs4072111C/T、rs4778889T/C三个位点的基因型与肝癌的患病风险无相关性(P>0.05)。
7.无论是在HBV携带人群中还是在非HBV携带人群中,IL-16 rs11556218T/G、rs4072111C/T、rs4778889T/C三个位点的基因型与肝癌的患病风险无相关性(P>0.05)。
8. GTC单倍型在肝癌组中的频率显著低于在对照组中的频率,GTC单倍型患肝癌的风险显著减低至0.02(P=0.03),提示GTC单倍型有可能是肝癌的一个保护因素。其他单倍型与肝癌的患病风险无相关性(P>0.05)。
结论:IL-16 rs4778889T/C位点TC基因型与肝癌的遗传易感性相关,TC基因型患肝癌的风险显著降低至0.50倍,说明TC基因型有可能是肝癌的一个保护因素。IL-16三个SNP的频率在对照组中的分布与华西地区、北京和日本等地研究的结果较类似,与美国犹他州、尼日利亚人群等研究的结果差异较大。GTC单倍型患肝癌的风险显著减低至0.02,提示GTC单倍型有可能是肝癌的一个保护因素。
Objectives To study polymorphisms between rs11556218T / G, rs4778889T/C and rs4072111C/T of interleukin -16 (IL-16) gene. To reveal the association between polymorphisms of IL-16 and hepatocellular carcinoma in GuangXi population. To obtain the important SNP or haplotype which was associated with the susceptibility to hepatocellular carcinoma, providing new genetic markers for the prevention of hepatocellular carcinoma and new target for the treatment of hepatocellular carcinoma.
Methods Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) strategy and DNA sequencing methods were used to analyze polymorphisms of IL-16 in 141 patients with HCC and age, sex-matched 142 healthy controls. Usingχ~2 test to exam the differences of genotype, allele, haplotype between the HCC group and control group, logstic regression was used to analysis odds ratio (Oddsratios, OR) and 95% CI(Confidence Intervals, CI), adjusted for sex and age by the logistic regression model, analysis the association between SNPs of polymorphisms and hepatocellular carcinoma. All the results were analyzed by SPSS 13.0. Using PLINK software to construct the haplotypes and analyzed.
Results
1. The differences of gender and age composition between HCC group and control group were not statistically significant(P>0.05). Genotype of IL-16 rs11556218T / G, rs4072111C / T, rs4778889T / C in HCC group and control group were consistent with Hardy-weinberg equilibrium, the samples detected were representative and comparable.
2. There were TT, TG and GG three genotypes in IL-16 rs11556218T / G, the difference of the frequency distribution between the two groups was no statistically significant (P =0.97). Comparing with TT genotype, TG genotype was not associated with susceptibility to hepatocellular carcinoma (P = 0.38), GG genotype was not associated with susceptibility to hepatocellular carcinoma (P =0.90). The genetic polymorphism of IL-16 rs11556218T / G was not associated with susceptibility to hepatocellular carcinoma.
3. There were CC, CT and TT three genotypes in IL-16 rs4072111C/T, the difference of the frequency distribution between the two groups was no statistically significant (P = 0.59). Comparing with CC genotype, CT genotype was not associated with susceptibility to hepatocellular carcinoma (P = 0.46), TT genotype was not associated with susceptibility to hepatocellular carcinoma (P =0.64). The genetic polymorphism of IL-16 rs4072111C/T was not associated with susceptibility to hepatocellular carcinoma.
4. There were TT, TC and CC three genotypes in IL-16 rs4778889T / C, the difference of the frequency distribution between the two groups was no statistically significant (P = 0.12). Comparing with TT genotype, TC genotype was associated with susceptibility to hepatocellular carcinoma(P=0.04), CC genotype was no associated with susceptibility to hepatocellular carcinoma (P =0.59). Comparing with TT genotype, the risk of patients carrying TC genotype developing hepatocellular carcinoma was significantly reduced to 0.5. The TC genotype maybe a protective factor for hepatocellular carcinoma.
5. The distribution of the three SNPs in the control group were similar to the findings from the west regions of China, Beijing and Japan, but there were differences when compared with the Utah of United States and Nigeria.
6. Both in the male and female population, the three SNPs of IL-16 were not associated with susceptibility to hepatocellular carcinoma (P>0.05).
7. Both in HBV carriers and non-HBV carrier population, the three SNPs of IL-16 were not associated with susceptibility to hepatocellular carcinoma (P>0.05).
8. The GTC haplotype frequency in the HCC group was significantly lower than that in the control group. The risk of patients carrying the GTC developing hepatocellular carcinoma was significantly reduced to 0.02. The GTC haplotype maybe a protective factor for hepatocellular carcinoma. The other haplotypes were not associated with susceptibility to hepatocellular carcinoma (P>0.05).
Conclution The rs4778889T/C polymorphism of TC genotype was significantly associated with the susceptibility to HCC. The risk of patients carrying TC genotype developing hepatocellular carcinoma was significantly reduced to 0.5. The TC genotype maybe a protective factor for hepatocellular carcinoma. The distribution of the three SNPs in the control group were similar to the findings from the west regions of China, Beijing and Japan, but there were differences when compared with the Utah of United States and Nigeria. The risk of patients carrying the GTC developing hepatocellular carcinoma was significantly reduced to 0.02. The GTC haplotype maybe a protective factor for hepatocellular carcinoma.
引文
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