Insertion/deletion polymorphisms in the promoter region of BRM contribute to risk of hepatocellular carcinoma in Chinese populations.
Insertion/deletion polymorphisms in the promoter region of BRM contribute to risk of hepatocellular carcinoma in Chinese populations.
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BRM 启动子区插入/缺失多态性导致中国人群发生肝细胞癌的风险
DOI：
10.1371/journal.pone.0055169
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Gao X;Huang M;Liu L;He Y;Yu Q;Zhao H;Zhou C;Zhang J;Zhu Z;Wan J;Jiang X;Gao Y
BRM（Brahma同源物）因其在肿瘤抑制和癌症发展中的关键作用而广为人知。BRM启动子区域的基因变异被认为与BRM表达缺失和肺癌风险相关。据作者所知，尚未有关于BRM基因多态性在肝细胞癌（HCC）风险中作用的研究。
在两项包含796例HCC病例和806例无癌个体的独立病例 - 对照研究中，我们使用基于PCR的方法对中国人群中BRM启动子区域内的两个假定功能性插入/缺失（indel）多态性[BRM - 1321（rs3832613）和BRM - 741（rs34480940）]进行了基因分型。实时逆转录 - 聚合酶链反应（RT - PCR）分析用于探究这些多态性与组织样本和HCC细胞系中BRM表达之间的基因型 - 表型相关性。逻辑回归分析显示，与BRM - 1321缺失/缺失基因型相比，插入/缺失和插入/插入变异基因型的HCC风险增加[调整后的比值比（OR）= 1.47，95%置信区间（CI）= 1.19 - 1.82；调整后的OR = 2.55，95% CI = 1.75 - 3.72]。未观察到BRM - 741与HCC发病率之间存在显著关联。然而，分层分析显示，在吸烟者中，BRM - 741的插入/插入基因型与HCC易感性增加之间存在显著关联（调整后的OR = 2.07，95% CI = 1.33 - 3.22）。定量PCR分析表明，BRM - 1321的基因型以及相应的单倍型与体内BRM表达显著相关。与插入/插入基因型相比，携带插入/缺失和缺失/缺失基因型的受试者在HCC组织样本中的BRM表达分别高2.30倍和4.99倍。在蛋白质水平的蛋白质印迹分析中也观察到了类似的趋势。
我们的研究结果表明，BRM启动子多态性（BRM - 1321）能够调节BRM表达，并可能作为HCC遗传易感性的潜在标志物。
Background BRM (Brahma homologue) is well known for its critical role in tumor suppression and cancer development. Genetic variations in the promoter region of BRM have been suggested to be associated with loss of BRM expression and lung cancer risk. To the authors’ knowledge, no study on the role of BRM genetic polymorphisms in hepatocellular carcinoma (HCC) risk has been performed. Methodology/Principal Findings In two independent case-control studies containing 796 HCC cases and 806 cancer-free individuals, we genotyped two putative functional insertion/deletion (indel) polymorphisms [BRM-1321 (rs3832613) and BRM-741 (rs34480940)] within promoter region of BRM in Chinese populations using a PCR-based method. Real-time RT-PCR analysis was used to explore the genotype-phenotype correlation between these polymorphisms and BRM expression in both tissue samples and HCC cell lines. Logistic regression analysis showed that compared to BRM-1321del/del genotype, the ins/del and ins/ins variant genotypes had an increased HCC risk [adjusted odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.19–1.82; adjusted OR = 2.55, 95% CI = 1.75–3.72, respectively]. No significant association between BRM-741 and HCC incidence was observed. However, stratification analysis revealed a significant association between ins/ins genotype of BRM-741 and increased HCC susceptibility in smokers (adjusted OR = 2.07, 95% CI = 1.33–3.22). Quantitative PCR analyses demonstrated that the genotypes of BRM-1321 and the corresponding haplotypes were significantly correlated with BRM expression in vivo. Compared with ins/ins genotype, subjects carrying ins/del and del/del genotype had 2.30 and 4.99 fold higher BRM expression in HCC tissue samples, respectively. Similar trends were observed in western blot analysis at protein level. Conclusions/Significance Our findings suggest that BRM promoter polymorphism (BRM-1321) could regulate BRM expression and may serve as a potential marker for genetic susceptibility to HCC.
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影响因子：
11.2
作者：
Banine, F;Bartlett, C;Sherman, LS
通讯作者：
Sherman, LS
DOI：
10.1097/00129039-200503000-00011
发表时间：
2005-03-01
影响因子：
1.6
作者：
Reisman, DN;Sciarrotta, J;Funkhouser, WK
通讯作者：
Funkhouser, WK
影响因子：
11.2
作者：
Sakurai, Kouhei;Furukawa, Chihiro;Iba, Hideo
通讯作者：
Iba, Hideo
影响因子：
8
作者：
Glaros, S.;Cirrincione, G. M.;Reisman, D.
通讯作者：
Reisman, D.
影响因子：
3.9
作者：
Medina, Pedro P.;Romero, Octavio A.;Sanchez-Cespedes, Montse
通讯作者：
Sanchez-Cespedes, Montse