Association of PNPLA3 with non-alcoholic fatty liver disease in a minority cohort: the Insulin Resistance Atherosclerosis Family Study

作者：Wagenknecht Lynne E^*; Palmer Nicholette D; Bowden Donald W; Rotter Jerome I; Norris Jill M; Ziegler Julie; Chen Yii Der I; Haffner Steven; Scherzinger Ann; Langefeld Carl D

来源：Liver International, 2011, 31(3): 412-416.

DOI：10.1111/j.1478-3231.2010.02444.x

• African Americans
• computed tomography
• genetic epidemiology
• hepatic steatosis
• Hispanic Americans
• non-alcoholic fatty liver disease
• PNPLA3

Background
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.
Aims
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).
Methods
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.
Results
Single nucleotide polymorphism (SNP) rs738409 was strongly associated with reduced liver density (i.e. NAFLD) in Hispanic Americans (1.18 x 10-9) and in African Americans (P=4.99 x 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.
Conclusions
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.

• 出版日期2011-3
• 单位河北医科大学