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- Title
Variation in Liver Enzymes Share Common Genetic Determinants with Features of the Metabolic Syndrome and Insulin Secretion.
- Authors
Guo, Xiuqing; Cui, Jinrui; Hsu, Fang-Chi; Haffner, Steven; Norris, Jill M.; Rich, Steve S.; Wagenknecht, Lynne E.; Rotter, Jerome I.; Chen, Y.-D. I.
- Abstract
Non-alcoholic fatty liver disease (NAFLD) is a potentially progressive disorder associated with insulin resistance and the metabolic syndrome (MS). Elevated liver enzyme (LE) levels have been related to features of the MS as well as to increased risk of cardiovascular and liver diseases. Family studies have shown that both the MS and LEs are heritable. However, it is still not clear whether there are any common genetic determinants linking these phenotypes. We investigate here the heritability of LEs and coheritability between LEs and components of the MS, and with insulin secretion. 1017 non-diabetic individuals from 88 large Hispanic American (HA) families were recruited at two clinical sites (San Antonio, TX and San Luis Valley, CO). Three liver enzymes: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were measured. Glucose homeostasis measures including the acute insulin response (AIR) and disposition index (DI) were determined by minimal model analysis of a frequently sampled intravenous glucose tolerance test. A variance component approach was used to estimate heritabilities and correlations (genetic and environmental). The likelihood ratio test was used to determine the significance of a genetic, environmental and/or phenotypic correlations. All the 3 LEs were heritable, with an estimated heritability±SE of 0.19±0.06 for AST, 0.30±0.07 for ALT, and 0.43±0.08 for GGT (p<0.0001 for each). After adjusting for age, sex, and BMI, AST was found to share common genetic determinants with BMI (genetic correlation and p values are: rG=- 0.41, p=0.004), DI (rG=0.45, p=0.02), and AIR (rG=0.43, p=0.009); while ALT was shown to cosegregate with fasting insulin (rG=0.64, p=0.0003), TG (rG=0.38, p=0.009), and AIR (rG=0.38, p=0.006). All 3 enzymes exhibited environmental correlations with MS components and insulin secretion; however in contrast to AST and ALT, no significant genetic correlations were observed with GGT. In conclusion, liver enzymes are heritable traits in non-diabetic HA. Both AST and ALT share common genetic determinants with features of the MS and insulin secretion, while GGT was correlated with these phenotypes mainly due to environmental effects.
- Subjects
LIVER diseases; INSULIN resistance; METABOLIC syndrome; CARDIOVASCULAR diseases; INSULIN; ASPARTATE aminotransferase; ALANINE aminotransferase; GLUCOSE
- Publication
Diabetes, 2007, Vol 56, pA244
- ISSN
0012-1797
- Publication type
Article