Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance.

TitleDissociation between APOC3 variants, hepatic triglyceride content and insulin resistance.
Publication TypeJournal Article
Year of Publication2011
AuthorsKozlitina, J, Boerwinkle, E, Cohen, JC, Hobbs, HH
JournalHepatology
Volume53
Issue2
Pagination467-74
Date Published2011 Feb
ISSN1527-3350
KeywordsAdult, African Americans, Apolipoprotein C-III, Body Mass Index, European Continental Ancestry Group, Female, Gene Frequency, Genetic Variation, Genotype, Heterozygote, Hispanic Americans, Humans, Insulin Resistance, Liver, Male, Middle Aged, Triglycerides
Abstract

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is an escalating health problem that is frequently associated with obesity and insulin resistance. The mechanistic relationship between NAFLD, obesity, and insulin resistance is not well understood. A nonsynonymous variant in patatin-like phospholipase domain containing 3 (rs738409, I148M) has been reproducibly associated with increased hepatic triglyceride content (HTGC) but has not been associated with either the body mass index (BMI) or indices of insulin resistance. Conversely, two sequence variants in apolipoprotein C3 (APOC3) that have been linked to hypertriglyceridemia (rs2854117 C > T and rs2854116 T > C) have recently been reported to be associated with both hepatic fat content and insulin resistance. Here we genotyped two APOC3 variants in 1228 African Americans, 843 European Americans and 426 Hispanics from a multiethnic population based study, the Dallas Heart Study and test for association with HTGC and homeostatic model of insulin resistance (HOMA-IR). We also examined the relationship between these two variants and HOMA-IR in the Atherosclerosis Risk in Communities (ARIC) study. No significant difference in hepatic fat content was found between carriers and noncarriers in the Dallas Heart Study. Neither APOC3 variant was associated with HOMA-IR in the Dallas Heart Study; this lack of association was confirmed in the ARIC study, even after the analysis was restricted to lean (BMI < 25 kg/m(2) ) individuals (n = 4399).CONCLUSION: Our data do not support a causal relationship between these two variants in APOC3 and either HTGC or insulin resistance in middle-aged men and women.

DOI10.1002/hep.24072
Alternate JournalHepatology
PubMed ID21274868
PubMed Central IDPMC3057507
Grant ListP01 HL020948 / HL / NHLBI NIH HHS / United States
P01 HL020948-34 / HL / NHLBI NIH HHS / United States
RL1 HL092550-04 / HL / NHLBI NIH HHS / United States
RL1 HL092550-05 / HL / NHLBI NIH HHS / United States
RL1 HL092550 / HL / NHLBI NIH HHS / United States
1RL1HL092550 / HL / NHLBI NIH HHS / United States
P01 HL20948 / HL / NHLBI NIH HHS / United States
R01 DK090066 / DK / NIDDK NIH HHS / United States