非酒精性脂肪肝：1个基因增加患病风险，1个基因能避免脂肪肝
2008难9月26日，新发现的基因变体解释了为什么拉美裔人，至少是非洲裔美国人易患脂肪肝。
在美洲和欧洲，非酒精性脂肪肝是一种很普遍的肝脏疾病。10个人有一个进行肝移植，三分之一的美国人有脂肪肝。
你可能知道，肥胖和症候簇聚是与非酒精性脂肪肝有关的代谢综合症。但是只有一部分人有患上这些症状的可能。
有一个发现是一部分人比其他人更容易患上脂肪肝，这种特质和祖先有关。脂肪肝患者中欧裔美国人占33%，西班牙美国人占45%，非裔美国人占24%。
Helen H. Hobbs是堪萨斯大学西南医学中心临床遗传学的主人，他带领研究者们，在2000多个参与者中需找基因变异体。
这个研究团队检测了1万两千多个基因变异体。最终，只有一个基因和脂肪肝有关系，这个基因叫做PNPLA3，它有着未知的功能。
这个基因变异体和脂肪肝有关。在49%的西班牙美国，23%的欧洲美国人和17的非洲美国人身上发现这个变异体。
分析显示这个基因解释了72%的遗传差异。有趣的是，基因差异也与肝炎有关系，也肯能通向其他更严重的疾病。
"最近，我们不能准确的预测，脂肪肝患者将发展成什么更严重的疾病，也不能知晓脂肪肝变成肝纤维化、发生肝损伤的过程。"Hobbs和他的同事提到，"这个基因变异体使得机体更容易发生肝损伤。"
显然，这种与脂肪肝有关的基因变异体使得PNPLA3基因的功能不为人所指或者知之甚少。
另外一个PNPLA3基因变体会使得脂肪肝的患病率很低，有助于PNPLA3基因更好的发挥功效。
原文：
Fatty Liver Disease: Genes Affect Risk
Nonalcoholic Fatty Liver Disease: 1 Gene Increases Risk, 1 Gene Protects
Sept. 26, 2008 -- Newly discovered gene variants explain why Hispanics are most likely -- and African-Americans are least likely -- to have fatty livers.
Nonalcoholic fatty liver disease (NAFLD) is the most common liver ailment in the U.S. and in Europe. It's behind one in 10 liver transplants. About a third of Americans have fatty livers, a step on the path to NAFLD.
As one might think, obesity and the cluster of symptoms known as the metabolic syndrome are linked to NAFLD. Yet some people with these risk factors get the disease while others don't.
A clue comes from the fact that some people are much more prone to liver fat than others. And this predisposition is linked to one's ancestry. Fatty livers occur in 33% of European-Americans, 45% of Hispanic-Americans, and 24% of African-Americans.
Researchers led by Helen H. Hobbs, MD, chief of clinical genetics at the University of Texas Southwestern Medical Center, looked for genetic variations in more than 2,000 participants in the Dallas Heart Study.
The team detected more than 12,000 gene variants. In the end, only one gene was linked to liver fat: a gene with unknown function called PNPLA3.
A variant version of this gene was strongly linked to fatty liver. The variant was seen in 49% of Hispanic-Americans, 23% of European-Americans, and 17% of African-Americans in the study.
Analysis showed that the gene explains 72% of the ancestry-related differences in liver fat. Interestingly, this gene variant was also linked to liver inflammation -- possibly the next step on the way to serious disease.
"Currently, we cannot accurately predict which individuals with fatty liver will develop [serious liver disease] and progress to cirrhosis and liver failure," Hobbs and colleagues note. "This gene variant may confer increased susceptibility to [liver] injury."
Apparently, the gene variant linked to liver fat makes the PNPLA3 gene function poorly or not at all.
Another PNPLA3 gene variant -- seen much more often in African-Americans than in Americans of other ancestry -- is linked to lower risk of liver fat. This gene variant appears to make the PNPLA3 gene work better.
The study appears in the Sept. 26 advance online issue of Nature Genetics.
