A genetic contribution to circulating cytokines and obesity in children.
Cytokines are considered to be involved in obesity-related metabolic diseases. Study objectives are to determine the heritability of circulating cytokine levels, to investigate pleiotropy between cytokines and obesity traits, and to present genome scan results for cytokines in 1030 Hispanic children enrolled in VIVA LA FAMILIA Study. Cytokine phenotypes included monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor beta 1 (TGF-beta1), C-reactive protein (CRP), regulated upon activation, normal T-cell expressed and secreted (RANTES) and eotaxin. Obesity-related phenotypes included body mass index (BMI), fat mass (FM), truncal FM and fasting serum insulin. Heritabilities ranged from 0.33 to 0.97. Pleiotropy was observed between cytokines and obesity traits. Positive genetic correlations were seen between CRP, leptin, MCP-1 and obesity traits, and negative genetic correlations with adiponectin, ICAM-1 and TGF-beta1. Genome-wide scan of sICAM-1 mapped to chromosome 3 (LOD=3.74) between markers D3S1580 and D3S1601, which flanks the adiponectin gene (ADIPOQ). Suggestive linkage signals were found in other chromosomal regions for other cytokines. In summary, significant heritabilities for circulating cytokines, pleiotropy between cytokines and obesity traits, and linkage for sICAM-1 on chromosome 3q substantiate a genetic contribution to circulating cytokine levels in Hispanic children.
Cai
Guowen
G
USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030, USA.
Cole
Shelley A
SA
Butte
Nancy F
NF
Smith
C Wayne
CW
Mehta
Nitesh R
NR
Voruganti
V Saroja
VS
Proffitt
J Michael
JM
Comuzzie
Anthony G
AG
D000293:Adolescent; D000818:Animals; D000886:Anthropometry; D001823:Body Composition / Q000235:genetics; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood* / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D009765:Obesity / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D055815:Young Adult
D016207:Cytokines