Department of Medicine II, Saarland University Hospital, Homburg, Germany.
Curr Opin Gastroenterol. 2011 May;27(3):231-9. doi: 10.1097/MOG.0b013e3283444862.
Recent advancements in genotyping technology have contributed to an accelerated dissemination of information on sequence variation associated with hepatobiliary diseases and/or quantitative traits.
Since the first genome-wide association study (GWAS) on genetic gallstone risk in 2007, a total of more than 25 GWAS related to the field have been reported. The identification of the IL-28B genotype as a critical host factor of natural and treatment-related outcomes in hepatitis C virus infection opens the avenue of personalized medicine and individual risk assessment by genetic information. By contrast, the second recent top-hit variant adiponutrin (PNPLA3) associated with liver fat content and fibrosis progression illustrates the potential of GWAS to identify novel pathobiological pathways. Another emerging research topic is in the designation of genetic markers for specific cirrhosis-related complications, such as spontaneous bacterial peritonitis (NOD2) and hepatic encephalopathy (glutaminase), of potential future relevance in prioritizing patients for preemptive treatment strategies.
In this article we critically discuss new concepts in the genetics of hepatobiliary diseases with a special focus on the advantages and limitations of the GWAS approach. An update on relevant recent GWAS and selected candidate gene study data will be given.
近年来基因分型技术的进步加速了与肝胆疾病和/或数量性状相关的序列变异信息的传播。
自 2007 年首次进行关于遗传胆石病风险的全基因组关联研究（GWAS）以来，已有超过 25 项与该领域相关的 GWAS 被报道。IL-28B 基因型被确定为丙型肝炎病毒感染自然和治疗相关结果的关键宿主因素，为通过遗传信息进行个体化医学和个体风险评估开辟了道路。相比之下，第二个最近的顶级变异体脂联素（PNPLA3）与肝脂肪含量和纤维化进展相关，说明了 GWAS 识别新的病理生物学途径的潜力。另一个新兴的研究课题是指定与特定肝硬化相关并发症相关的遗传标记，例如自发性细菌性腹膜炎（NOD2）和肝性脑病（谷氨酰胺酶），这些标记在为预防性治疗策略确定患者优先级方面具有潜在的未来相关性。
本文我们批判性地讨论了肝胆疾病遗传学的新概念，特别关注 GWAS 方法的优势和局限性。将提供相关最近 GWAS 和选定候选基因研究数据的更新。
