Federico Oldoni (United States of America)
University of Texas Southwestern Medical Center Molecular GeneticsAuthor Of 1 Presentation
O021 - Genetic and Metabolic Determinants of Plasma Levels of ANGPTL8 (ID 202)
Abstract
Background and Aims
Angiopoietin-like protein (ANGPTL)8 (A8), together with A3 and A4, coordinate changes in triglyceride (TG) delivery to tissues in response to nutritional status. Plasma A8 levels are associated with indices of glucose and TG metabolism, but the causality of these relationships and the contribution of genetic variants to inter-individual differences in A8 levels has not been investigated.
Methods
To address these questions, we developed a sensitive and specific A8 ELISA and measured plasma A8 levels in the Dallas Heart Study (DHS), a large multiethnic population-based cohort.
Results
The distribution of fasting A8 levels was highly skewed to the right with a median (IQR) of 13.3 (6.8–23.1) ng/mL. A8 levels did not differ significantly across age groups or genders. Remarkable differences were found among racial/ethnic groups with Blacks having significantly higher A8 levels than either Hispanics or Whites. A8 levels correlated with BMI, fasting glucose, insulin and TG levels. Exome-wide association study revealed a strong association between the minor T-allele of the A8(R59W) variant with plasma A8 levels. After adjustment for age, sex, race/ethnicity and BMI, the A8(59W) variant explained ~17% of the inter-individual variation in A8 levels. This variant was not associated with any of the metabolic parameters correlated with plasma A8 concentrations despite resulting in a 4-fold increase in A8 levels.
Conclusions
A8 levels are a consequence, not the cause, of the associated metabolic phenotypes.
Presenter of 1 Presentation
O021 - Genetic and Metabolic Determinants of Plasma Levels of ANGPTL8 (ID 202)
Abstract
Background and Aims
Angiopoietin-like protein (ANGPTL)8 (A8), together with A3 and A4, coordinate changes in triglyceride (TG) delivery to tissues in response to nutritional status. Plasma A8 levels are associated with indices of glucose and TG metabolism, but the causality of these relationships and the contribution of genetic variants to inter-individual differences in A8 levels has not been investigated.
Methods
To address these questions, we developed a sensitive and specific A8 ELISA and measured plasma A8 levels in the Dallas Heart Study (DHS), a large multiethnic population-based cohort.
Results
The distribution of fasting A8 levels was highly skewed to the right with a median (IQR) of 13.3 (6.8–23.1) ng/mL. A8 levels did not differ significantly across age groups or genders. Remarkable differences were found among racial/ethnic groups with Blacks having significantly higher A8 levels than either Hispanics or Whites. A8 levels correlated with BMI, fasting glucose, insulin and TG levels. Exome-wide association study revealed a strong association between the minor T-allele of the A8(R59W) variant with plasma A8 levels. After adjustment for age, sex, race/ethnicity and BMI, the A8(59W) variant explained ~17% of the inter-individual variation in A8 levels. This variant was not associated with any of the metabolic parameters correlated with plasma A8 concentrations despite resulting in a 4-fold increase in A8 levels.
Conclusions
A8 levels are a consequence, not the cause, of the associated metabolic phenotypes.