长非编码 RNA HULC 中的一个遗传变异与中国人群乙型肝炎病毒相关肝细胞癌的风险相关。
A genetic variant in long non-coding RNA HULC contributes to risk of HBV-related hepatocellular carcinoma in a Chinese population.
机构信息
Department of Epidemiology and biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
出版信息
PLoS One. 2012;7(4):e35145. doi: 10.1371/journal.pone.0035145. Epub 2012 Apr 6.
BACKGROUND
Recently, several studies have demonstrated that two long non-coding RNAs (lncRNAs), HULC and MALAT1, may participate in hepatocellular carcinoma (HCC) development and progression. However, genetic variations in the two lncRNAs and their associations with HCC susceptibility have not been reported. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) in HULC and MALAT1 may contribute to HCC risk.
METHODS
We conducted a case-control study and genotyped two SNPs, rs7763881 in HULC and rs619586 in MALAT1, in 1300 HBV positive HCC patients, 1344 HBV persistent carriers and 1344 subjects with HBV natural clearance to test the associations between the two SNPs and susceptibility to HCC and HBV chronic infection.
RESULTS
The variant genotypes of rs7763881 were significantly associated with decreased HCC risk in a dominant genetic model [AC/CC vs. AA: adjusted odds ration (OR) = 0.81, 95% confidence intervals (CIs) = 0.68-0.97, P = 0.022]. Furthermore, the variant genotypes of rs619586 was associated with decreased HCC risk with a borderline significance (AG/GG vs. AA: adjusted OR = 0.81, 95% CIs = 0.65-1.01, P = 0.057). However, no significant association was found between the two SNPs and HBV clearance.
CONCLUSIONS
The variant genotypes of rs7763881 in HULC may contribute to decreased susceptibility to HCC in HBV persistent carriers.
背景
最近，几项研究表明，两个长非编码 RNA（lncRNA），HULC 和 MALAT1，可能参与肝癌（HCC）的发展和进展。然而，这两个 lncRNA 的遗传变异及其与 HCC 易感性的关系尚未报道。在这项研究中，我们假设 HULC 和 MALAT1 中的单核苷酸多态性（SNP）可能导致 HCC 风险。
方法
我们进行了一项病例对照研究，对 1300 例 HBV 阳性 HCC 患者、1344 例 HBV 持续携带者和 1344 例 HBV 自然清除者中的两个 SNP（HULC 中的 rs7763881 和 MALAT1 中的 rs619586）进行基因分型，以检验这两个 SNP 与 HCC 和 HBV 慢性感染易感性之间的关系。
结果
在显性遗传模型中，rs7763881 的变异基因型与 HCC 风险降低显著相关[AC/CC 与 AA：调整后的优势比（OR）=0.81，95%置信区间（CI）=0.68-0.97，P=0.022]。此外，rs619586 的变异基因型与 HCC 风险降低也有相关性，但具有边缘显著性（AG/GG 与 AA：调整后的 OR=0.81，95%CI=0.65-1.01，P=0.057）。然而，这两个 SNP 与 HBV 清除之间没有显著的关联。
结论
HULC 中的 rs7763881 变异基因型可能导致 HBV 持续携带者 HCC 易感性降低。
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