Submitted to: International Journal of Obesity
Publication Type: Peer reviewed journal
Publication Acceptance Date: 6/2/2006
Publication Date: 3/1/2007
Citation: Tejero, M.E., Cai, G., Goring, H.H.H., Diego, V., Cole, S.A., Bacino, C.A., Butte, N.F., Comuzzie, A.G. 2007. Linkage analysis of circulating levels of adiponectin in Hispanic children. International Journal of Obesity. 31(3):535-542. Interpretive Summary: Adiponectin is a hormone produced exclusively by fat tissue and has insulin-sensitizing and anti-inflammatory properties. In contrast to other fat tissue products, low circulating levels of this hormone are associated with obesity, type 2 diabetes, and the metabolic syndrome. The aim of this study was to find chromosomal regions, referred to as quantitative trait loci (QTLs), that affect blood levels of adiponectin in Hispanic children participating in the VIVA LA FAMILIA Study. Adiponectin was measured by radioimmunoassay (RIA) technique in 466 children from 127 families. Using a genome scan and variance decomposition analysis, we localized two chromosomal regions that contain gene(s) influencing blood levels of adiponectin. One signal was on chromosome 11q23.2-11q24.2, (LOD=4.2) and a second significant signal (LOD score = 3.0) was found on chromosome 8q12.1-8q21.3. Although the region on chromosome 11 has been associated with obesity and diabetes-related traits in adult populations, this is the first observation of linkage in this chromosomal region for adiponectin levels. In conclusion, the strong linkage signal on chromosome 11 for adiponectin most likely harbors a gene(s) which may contribute to the high susceptibility of these Hispanic children to obesity and type 2 diabetes.
Technical Abstract: Adiponectin, a hormone produced exclusively by adipose tissue, is inversely associated with insulin resistance and pro-inflammatory conditions. The aim of this study was to find quantitative trait loci (QTLs) that affect circulating levels of adiponectin in Hispanic children participating in the VVA LA FAMILIA Study by use of a systematic genome scan. The present study included extended families with at least one overweight child between 4 to 19 years old. Overweight was defined as BMI 95th percentile. Fasting blood was collected from 466 children from 127 families. Adiponectin was assayed by radioimmunoassay (RIA) technique in fasting serum. A genome wide scan on circulating levels of adiponectin as a quantitative phenotype was conducted using the variance decomposition approach. The highest LOD score (4.2) was found on chromosome 11q23.2-11q24.2, and a second significant signal (LOD score = 3.0) was found on chromosome 8q12.1-8q21.3. In addition, a signal suggestive of linkage (LOD score = 2.5) was found between 18q21.3-18q22.3 After adjustment for BMI-Z score the LOD score on chromosome 11 remained unchanged, but the signals on chromosomes 8 and 18 dropped to 1.6 and 1.7, respectively. Two other signals suggestive of linkage were found on chromosome 3 (LOD score = 2.1) and 10 (LOD score = 2.5). Although the region on chromosome 11 has been associated with obesity and diabetes-related traits in adult populations, this is the first observation of linkage in this region for adiponectin levels. Our suggestive linkages on chromosome 10 and 3 replicate results for adiponectin seen in other populations. The influence of loci on chromosomes 18 and 8 on circulating adiponectin seemed to be mediated by BMI in the present study. Our genome scan in children has identified a novel QTL and replicated QTLs in chromosomal regions previously shown to be linked with obesity and type 2 diabetes-related phenotypes in adults. The genetic contribution of loci to adiponectin levels may vary across different populations and age groups. The strong linkage signal on chromosome 11 is most likely underlain by a gene(s) which may contribute to the high susceptibility of these Hispanic children to obesity and type 2 diabetes.