Abstract P227: Direct Association of Adiponectin with Individual European Ancestry in African Americans: the Jackson Heart Study

Abstract

Background: Compared with European Americans, African Americans exhibit lower levels of the cardio-metabolically protective adipokine known as adiponectin even after accounting for adiposity measures. Few studies have examined the association between adiponectin and individual ancestry estimates in African Americans, and most of these studies used only a few hundreds of the ancestry informative markers (AIMs). Therefore, we employed a relatively dense panel of AIMs to estimate the individual proportions of European ancestry (PEA) for the African Americans enrolled in a large community-based cohort in order to test the hypothesis that plasma adiponectin and PEA are directly associated. Methods: Plasma specimens from 1,439 participants with available DNA in the Jackson Heart Study were analyzed by ELISA for adiponectin levels. Using pseudo-ancestral population genotype data from the International HapMap Consortium, PEA was estimated for each individual with a panel of up to 1,447 genome-wide preselected AIMs by a maximum likelihood approach. Insulin resistance, defined as the highest quartile, was estimated with the homeostasis model assessment of insulin resistance (HOMA-IR) and obesity by a body mass index (BMI) greater or equal to 30 kg/m 2 . Interaction assessment and stepwise linear regression models were used to analyze the cross-sectional association between adiponectin and PEA. A p-value less than 0.05 was considered significant for the main and the interactive effects. Results: Among the study participants (62% women; mean age 48 ± 12 years), the median (interquartile range) of PEA was 15.8 (9.3)%. BMI ( p = .0004 ) and insulin resistance ( p = .002 ) were effect modifiers of the assessed association, but not sex ( p = .31 ) or waist circumference ( p = .62 ). Among non-obese individuals (n = 673), adiponectin was directly associated with PEA (β = 3.3 ± 1.5, p = .03 ) after adjustment for age, sex, waist circumference, systolic blood pressure, HOMA-IR, cholesterol fractions, C-reactive protein, physical activity and, in the initial stepwise models, measures of socioeconomic status. Among participants without insulin resistance (n = 1,141), after adjustment for the same variables with the exception of age and HOMA-IR (as indicated by the stepwise procedure), a direct association between adiponectin and PEA was also observed (β = 4.4 ± 1.3, p = .0005 ). Conclusions: In a large community-based African American population, the individual proportion of the global European ancestry was directly associated with plasma adiponectin among participants without impaired lipid or glucose metabolism, namely among those without obesity or insulin-resistance. Our study results point to the genetic origins of the lower levels of adiponectin in African Americans and warrant further exploration of the role ancestry plays in the complex relationship of adiponectin with cardio-metabolic risk factors.