Abstract
BackgroundAdiponectin is inversely associated with obesity, insulin resistance, and atherosclerosis, but little is known about the genetic pathways that regulate the plasma level of this protein. To find novel genes that influence circulating levels of adiponectin, a genome-wide linkage scan was performed on plasma adiponectin concentrations before and after 3 weeks of treatment with fenofibrate (160 mg daily) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. We studied Caucasian individuals (n = 1121) from 190 families in Utah and Minnesota. Of these, 859 individuals from 175 families had both baseline and post-fenofibrate treatment measurements for adiponectin. Plasma adiponectin concentrations were measured with an ELISA assay. All participants were typed for microsatellite markers included in the Marshfield Mammalian Genotyping Service marker set 12, which includes 407 markers spaced at approximately 10 cM regions across the genome. Variance components analysis was used to estimate heritability and to perform genome-wide scans. Adiponectin was adjusted for age, sex, and field center. Additional models also included BMI adjustment.ResultsBaseline and post-fenofibrate adiponectin measurements were highly correlated (r = 0.95). Suggestive (LOD > 2) peaks were found on chromosomes 1p35.2 and 3q28 (near the location of the adiponectin gene).ConclusionTwo candidate genes, IL22RA1 and IL28RA, lie under the chromosome 1 peak; further analyses are needed to identify the specific genetic variants in this region that influence circulating adiponectin concentrations.
Highlights
Adiponectin is inversely associated with obesity, insulin resistance, and atherosclerosis, but little is known about the genetic pathways that regulate the plasma level of this protein
Adiponectin is hypothesized to be protective in the pathogenesis of atherosclerosis [7,8], perhaps by reducing activity of iNOS in the vascular adventia [9] or by reducing accumulation of lipids in macrophage foam cells [10]
Several studies have found circulating adiponectin to be heritable, with heritability estimates ranging from 0.42 to 0.93 [11,12,13,14,15], suggesting that genetic variants play a role in regulating adiponectin
Summary
Adiponectin is inversely associated with obesity, insulin resistance, and atherosclerosis, but little is known about the genetic pathways that regulate the plasma level of this protein. To find novel genes that influence circulating levels of adiponectin, a genome-wide linkage scan was performed on plasma adiponectin concentrations before and after 3 weeks of treatment with fenofibrate (160 mg daily) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. Several studies have found circulating adiponectin to be heritable, with heritability estimates ranging from 0.42 to 0.93 [11,12,13,14,15], suggesting that genetic variants play a role in regulating adiponectin To find these variants, several studies have performed whole-genome linkage scans to determine which areas of the genome may harbor genes influencing circulating adiponectin concentrations [1216]. Likely because of the diverse study populations used in each of these scans, few significant linkage results have been replicated across studies
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