Division of Public Health Sciences, Wake Forest University Baptist Medical Center, Winston-Salem, NC 27157, USA.
Liver Int. 2011 Mar;31(3):412-6. doi: 10.1111/j.1478-3231.2010.02444.x. Epub 2011 Jan 13.
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition, particularly among Hispanic Americans. A genetic variant in PNPLA3 (rs738409) has been identified as a strong predictor of hepatic fat content.
To confirm the association of this variant with NAFLD in two minority cohorts, Hispanic Americans and African Americans, in whom liver density was quantified by computed tomography (CT).
This analysis was conducted in the Insulin Resistance Atherosclerosis (IRAS) Family Study. Participants were recruited from the general community and included 843 Hispanic American and 371 African American adults aged 18-81 years. A single variant in PNPLA3 (rs738409) was genotyped. Liver density was calculated in Hounsfield Units from abdominal CT scans.
Single nucleotide polymorphism (SNP) rs738409 was strongly associated with reduced liver density (i.e. NAFLD) in Hispanic Americans (1.18 × 10⁻⁹) and in African Americans (P=4.99 × 10⁻⁶). The association followed an additive genetic model with the G allele conferring risk. The allele was two times more common in Hispanic Americans than in African Americans (40 vs 19%), consistent with the greater prevalence of NAFLD in Hispanic Americans (24 vs 9%). The SNP explained 4.4 and 5.6% of the variance of the adjusted liver density outcome in Hispanic Americans and African Americans, respectively.
We confirmed the association of a PNPLA3 variant with NAFLD in Hispanic Americans and African Americans, suggesting that PNPLA3 contributes to the variation in NAFLD across multiple ethnicities. This study adds to the growing evidence that some of the ethnic variation in NAFLD is genetic.
非酒精性脂肪性肝病（NAFLD）是一种高度流行的疾病，尤其在西班牙裔美国人中更为常见。PNPLA3（rs738409）的基因变异已被确定为肝内脂肪含量的强有力预测因子。
通过计算机断层扫描（CT）定量检测肝脏密度，在西班牙裔美国人和非裔美国人这两个少数族裔队列中证实该变异与 NAFLD 的关联。
本分析在胰岛素抵抗动脉粥样硬化（IRAS）家族研究中进行。研究对象来自普通社区，包括 843 名西班牙裔美国人和 371 名非裔美国人，年龄在 18-81 岁之间。检测了 PNPLA3 中的单个变异（rs738409）。从腹部 CT 扫描中计算肝脏密度的亨氏单位。
单核苷酸多态性（SNP）rs738409 与西班牙裔美国人（1.18×10⁻⁹）和非裔美国人（P=4.99×10⁻⁶）的肝脏密度降低（即 NAFLD）密切相关。该关联遵循加性遗传模式，G 等位基因赋予风险。该等位基因在西班牙裔美国人中比非裔美国人中更为常见（40%比 19%），这与西班牙裔美国人中 NAFLD 的更高患病率（24%比 9%）一致。该 SNP 分别解释了西班牙裔美国人和非裔美国人调整后的肝脏密度结果的 4.4%和 5.6%的方差。
我们在西班牙裔美国人和非裔美国人中证实了 PNPLA3 变异与 NAFLD 的关联，表明 PNPLA3 导致了多种族裔之间 NAFLD 的变化。这项研究增加了越来越多的证据，表明 NAFLD 的一些种族差异是遗传的。
