Suggestion for linkage of chromosome 1p35.2 and 3q28 to plasma adiponectin concentrations in the GOLDN Study.
BACKGROUND
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. 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.


RESULTS
Baseline 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).


CONCLUSIONS
Two 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.
Rasmussen-Torvik
Laura J
LJ
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA. rasm0218@umn.edu
Pankow
James S
JS
Peacock
James M
JM
Borecki
Ingrid B
IB
Hixson
James E
JE
Tsai
Michael Y
MY
Kabagambe
Edmond K
EK
Arnett
Donna K
DK
D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002878:Chromosomes, Human, Pair 1; D002893:Chromosomes, Human, Pair 3; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D008910:Minnesota; D014589:Utah; D044465:White People; D055815:Young Adult
C499918:ADIPOQ protein, human; D052242:Adiponectin; D000960:Hypolipidemic Agents; D011345:Fenofibrate