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[启动子区let-7基因多态性与肝细胞癌遗传易感性的关系]

[Relationship between genetic polymorphism of promoter region let-7 and genetic susceptibility to hepatocellular carcinoma].

作者信息

Huang Fang, Hu Ling-min, Liu Ji-bin, Zhang Yi-xin, Hu Zhi-bin

机构信息

School of Basic Medicine, Nantong University, Nantong 226001, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2011 Dec;45(12):1093-8.

Abstract

OBJECTIVE

The purpose of this study was to discuss the relationship between genetic polymorphism of promoter region let-7 and genetic susceptibility to hepatocellular carcinoma (HCC) in Chinese population.

METHODS

In this case-control study, 1300 cases of HBV positive patients were recruited in case group and another 1344 cases of persistent chronic HBV carriers were selected as control. 5 ml of blood sample was collected from each subject, from which the DNA was extracted; and rs10877887 and rs13293512 in promoter region let-7 were selected as the study sites. The polymorphism was detected by TaqMan allelic discrimination assay and the OR value (95%CI) was evaluated by Logistic Regression Method to analyze the relationship between susceptibility to HCC and different genotypes.

RESULTS

The frequencies of genotype TT, CT and CC in site rs10877887 were 43.0% (542/1261), 44.7% (564/1261) and 12.3% (155/1261) respectively in case group; while separately 44.0% (581/1319), 44.4% (585/1319) and 11.6% (153/1319)in control group. The frequencies of genotype TT, CT and CC in site rs13293512 were 32.0% (406/1270), 48.1% (611/1270) and 19.9% (253/1270) respectively in case group; while separately 33.1% (427/1291), 49.4% (638/1291) and 17.5% (226/1291) in control group. The results of multifactor logistic regression analysis showed no statistical significance in the relationship between different genotype TT, mutated genotype C in site rs10877887 and susceptibility to HCC (CC + CT vs TT, adjusted OR = 1.05, 95%CI: 0.90 - 1.23); and either no statistical significance in the relationship between different genotype TT, mutated genotype C in site rs13293512 and susceptibility to HCC (CC + CT vs TT, adjusted OR = 1.06, 95%CI: 0.89 - 1.25). The united-analysis of the two sites showed the frequencies of 0, 1, 2 and 3-4 mutated-genotype C were 13.3% (164/1235), 36.2% (447/1235), 33.0% (408/1235) and 17.5% (216/1235) respectively in case group; and separately 14.2% (181/1269), 37.0% (469/1269), 33.1% (420/1269) and 15.7% (199/1269) in control group. The susceptibility to HCC in 1,2,3-4 mutated-genotype C carriers were 1.05 (0.81 - 1.34), 1.07 (0.83 - 1.38) and 1.22 (0.91 - 1.62) times of the non-mutated genotype subjects; but there was no statistical significance (Wald χ(2) = 1.79, P = 0.181).

CONCLUSION

The polymorphism of study sites rs10877887 and rs13293512 may not be the biomarker of susceptibility to HCC in Chinese.

摘要

目的

本研究旨在探讨中国人群中let-7启动子区域基因多态性与肝细胞癌(HCC)遗传易感性之间的关系。

方法

在这项病例对照研究中,病例组招募了1300例HBV阳性患者,另选1344例持续性慢性HBV携带者作为对照组。从每个受试者采集5ml血液样本,从中提取DNA;选择let-7启动子区域的rs10877887和rs13293512作为研究位点。采用TaqMan等位基因鉴别分析检测多态性,并通过Logistic回归方法评估OR值(95%CI),以分析HCC易感性与不同基因型之间的关系。

结果

病例组中rs10877887位点的基因型TT、CT和CC频率分别为43.0%(542/1261)、44.7%(564/1261)和12.3%(155/1261);而对照组分别为44.0%(581/1319)、44.4%(585/1319)和11.6%(153/1319)。病例组中rs13293512位点的基因型TT、CT和CC频率分别为32.0%(406/1270)、48.1%(611/1270)和19.9%(253/1270);而对照组分别为33.1%(427/1291)、49.4%(638/1291)和17.5%(226/1291)。多因素Logistic回归分析结果显示,rs10877887位点不同基因型TT、突变基因型C与HCC易感性之间的关系无统计学意义(CC + CT vs TT,校正OR = 1.05,95%CI:0.90 - 1.23);rs13293512位点不同基因型TT、突变基因型C与HCC易感性之间的关系也无统计学意义(CC + CT vs TT,校正OR = 1.06,95%CI:0.89 - 1.25)。两个位点的联合分析显示,病例组中0、1、2和3 - 4个突变基因型C的频率分别为13.3%(164/1235)、36.2%(447/1235)、33.0%(408/1235)和17.5%(216/1235);对照组分别为14.2%(181/1269)、37.0%(469/1269)、33.1%(420/1269)和15.7%(199/1269)。1、2、3 - 4个突变基因型C携带者的HCC易感性是非突变基因型受试者的1.05(0.81 - 1.34)、1.07(0.83 - 1.38)和1.22(0.91 - 1.62)倍;但无统计学意义(Wald χ(2)=1.79,P = 0.181)。

结论

rs10877887和rs13293512研究位点的多态性可能不是中国人HCC易感性的生物标志物。

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