TY - JOUR
T1 - A genetic contribution to circulating cytokines and obesity in children
AU - Cai, Guowen
AU - Cole, Shelley A.
AU - Butte, Nancy F.
AU - Smith, C. Wayne
AU - Mehta, Nitesh R.
AU - Voruganti, V. Saroja
AU - Proffitt, J. Michael
AU - Comuzzie, Anthony G.
N1 - Funding Information:
We thank the families who participated in this study, and acknowledge the contributions of Mercedes Alejandro and Marilyn Navarrete for study coordination, and Sopar Seributra for nursing and Theresa Wilson, Tina Ziba, Maurice Puyau, Firoz Vohra, Anne Adolph, Roman Shypailo, JoAnn Pratt, and Maryse Laurent for technical assistance. This work is a publication of the US Department of Agriculture (USDA)/Agricultural Research Service (ARS) Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas. This project was funded with federal funds from the NIH R01 DK59264 and from USDA/ARS under Cooperative Agreement 58-6250-51000-037. This investigation was conducted in facilities constructed with support from Research Facilities Improvement Program Grants numbered C06 RR13556 and C06 RR017515 from the National Center for Research Resources, NIH.
PY - 2008/11
Y1 - 2008/11
N2 - 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-α), leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor beta 1 (TGF-β1), 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-β1. 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.
AB - 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-α), leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor beta 1 (TGF-β1), 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-β1. 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.
KW - Childhood obesity
KW - Cytokines
KW - Genome-wide scan
KW - Inflammation
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U2 - 10.1016/j.cyto.2008.08.006
DO - 10.1016/j.cyto.2008.08.006
M3 - Article
C2 - 18848781
AN - SCOPUS:55749109702
VL - 44
SP - 242
EP - 247
JO - Cytokine
JF - Cytokine
SN - 1043-4666
IS - 2
ER -