title: Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network.
abstract: OBJECTIVE
  Adiponectin is an adipose-secreted protein that has been linked to changes in insulin sensitivity, high-density lipoprotein cholesterol levels, and inflammatory patterns. Although fenofibrate therapy can raise adiponectin levels, treatment response is heterogeneous and heritable, suggesting a role for genetic mediators. This is the first genome-wide association study of fenofibrate effects on circulating adiponectin.
  
  
  RESULTS
  Plasma adiponectin was measured in participants of the Genetics of Lipid Lowering Drugs and Diet Network (n = 793) before and after a 3-week daily treatment with 160 mg of fenofibrate. Associations between variants on the Affymetrix Genome-Wide Human SNP Array 6.0 and adiponectin were assessed using mixed linear models, adjusted for age, sex, site, and family. We observed a statistically significant (P = 5 × 10⁻⁸) association between rs2384207 in 12q24, a region previously linked to several metabolic traits, and the fenofibrate-induced change in circulating adiponectin. Additionally, our genome-wide analysis of baseline adiponectin levels replicated the previously reported association with CDH13 and suggested novel associations with markers near the PCK1, ZBP1, TMEM18, and SCUBE1 genes. The findings from the single marker tests were corroborated in gene-based analyses. Biological pathway analyses suggested a borderline significant association between the EGF receptor signaling pathway and baseline adiponectin levels.
  
  
  CONCLUSIONS
  We present preliminary evidence linking several biologically relevant genetic variants to adiponectin levels at baseline and in response to fenofibrate therapy. Our findings provide support for fine-mapping of the 12q24 region to investigate the shared biological mechanisms underlying levels of circulating adiponectin and susceptibility to metabolic disease.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, RPHB 217G, Birmingham, AL 35294, USA. Electronic address: saslibek@uab.edu.
authors.forename: S
authors.initials: S
authors.lastname: Aslibekyan
authors.forename: P
authors.initials: P
authors.lastname: An
authors.forename: A C
authors.initials: AC
authors.lastname: Frazier-Wood
authors.forename: E K
authors.initials: EK
authors.lastname: Kabagambe
authors.forename: M R
authors.initials: MR
authors.lastname: Irvin
authors.forename: R J
authors.initials: RJ
authors.lastname: Straka
authors.forename: H K
authors.initials: HK
authors.lastname: Tiwari
authors.forename: M Y
authors.initials: MY
authors.lastname: Tsai
authors.forename: P N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: I B
authors.initials: IB
authors.lastname: Borecki
authors.forename: J M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: D K
authors.initials: DK
authors.lastname: Arnett
mesh_terms: D052242:Adiponectin / Q000097:blood* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002881:Chromosomes, Human, Pair 12; D004351:Drug Resistance; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008910:Minnesota; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D014589:Utah
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D015820:Cadherins; C099972:H-cadherin; D000960:Hypolipidemic Agents; D011345:Fenofibrate