Genome-wide linkage analysis for circulating levels of adipokines and C-reactive protein in the Quebec family study (QFS).
Adipose tissue synthesizes and secretes a wide range of biologically active molecules considered as inflammatory markers whose dysregulation in obesity plays a role in the development of insulin resistance and vascular disorders. Thus, finding genes that influence circulating levels of inflammatory biomarkers may provide insights into the genetic determinants of obesity-related metabolic diseases. We performed linkage analyses for fasting plasma levels of adiponectin, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor-necrosis factor-alpha (TNF-alpha) in 764 subjects enrolled in the Quebec family study (QFS). A maximum of 393 pairs of siblings from 211 nuclear families were available for analyses. A total of 443 markers spanning the 22 autosomal chromosomes with an average inter-marker distance of 6.24 Mb were genotyped. Linkage was tested using both allele-sharing (SIBPAL) and variance component linkage methods (MERLIN). We showed suggestive evidence of linkage for plasma adiponectin levels on chromosome 15q21.1 [D15S659; logarithm of the odds (LOD) score = 2.23], 3q13.33 (D3S3023; LOD = 2.09), 20q13.2 (D20S197; LOD = 1.96) and 14q32.2 (D14S1426; LOD = 1.79). Evidence of linkage (SIBPAL) was also found for CRP on 12p11.23 (P = 0.001) and 12q15 (P = 0.0005) and for IL-6 on 14q12 (P = 0.002). None of these linkages remained significant after adjustment for body mass index. No evidence of linkage was found for TNF-alpha plasma levels. These results suggest that several QTLs can influence plasma levels of adiponectin and CRP, partly via their effects on adiposity.
Ruchat
Stephanie-May
SM
Department of Preventive Medicine, Laval University, Quebec, Canada.|Lipid Research Center, CHUL Research Center, Quebec, Canada.
Després
Jean-Pierre
JP
Quebec Heart Institute, Hopital Laval Research Centre, Quebec, Canada.
Weisnagel
S John
SJ
Department of Preventive Medicine, Laval University, Quebec, Canada.|Lipid Research Center, CHUL Research Center, Quebec, Canada.
Chagnon
Yvon C
YC
Laval University Robert-Giffard Research Center, Beauport, QC, Canada.
Bouchard
Claude
C
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Pérusse
Louis
L
Department of Preventive Medicine, Laval University, Quebec, Canada. louis.perusse@kin.msp.ulaval.ca.|Lipid Research Center, CHUL Research Center, Quebec, Canada. louis.perusse@kin.msp.ulaval.ca.
D052242:Adiponectin / Q000097:blood* / Q000235:genetics*; D000328:Adult; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D040641:Quantitative Trait Loci; D011792:Quebec
D052242:Adiponectin; D005819:Genetic Markers; D002097:C-Reactive Protein