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Physiol. Genomics 19: 170-174, 2004. First published July 13, 2004; doi:10.1152/physiolgenomics.00122.2004
1094-8341/04 $5.00
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Received 25 May 2004; accepted in final form 7 July 2004.
Physiological Genomics 19:170-174 (2004)
1094-8341/04 $5.00 © 2004 American Physiological Society

Multigenic control of serum adiponectin levels: evidence for a role of the APM1 gene and a locus on 14q13

C. Menzaghi1, T. Ercolino2, L. Salvemini1, A. Coco1, S. H. Kim2, G. Fini1, A. Doria2 and V. Trischitta1,3

1 Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
2 Research Division Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts
3 Department of Clinical Sciences, University La Sapienza, Rome, Italy

Adiponectin is a circulating enhancer of insulin action that is secreted by the adipose tissue. In epidemiological studies, serum levels of this protein predict the risk of type 2 diabetes and cardiovascular events. Serum adiponectin levels have been associated with variants at the adiponectin (APM1) and PPAR{gamma}2 loci and have also been linked to markers on 5p15 and 14q13. We investigated the role of these four loci in regulating serum adiponectin in a Caucasian population from Italy. Four haplotype-tagging single-nucleotide polymorphisms (ht-SNPs) (–11377 C>G, –4041 A>C, +45 T>G, and +276 G>T) at the APM1 locus and the PPAR{gamma}2 Pro12Ala polymorphism were examined for association with serum adiponectin in 413 unrelated, nondiabetic individuals. Of the five SNPs tested, +276G>T was the only one to be associated with serum adiponectin ( P = 0.032), with "TT" individuals having higher adiponectin levels than other subjects. In a variance-components analysis of 737 nondiabetic members of 264 nuclear families, adiponectin heritability was 30%, with a small but significant proportion explained by the +276 genotype ( P = 0.0034). Suggestive evidence of linkage with adiponectin levels was observed on chromosome 14q13, with a LOD of 2.92 ( P = 0.000057) after including the APM1 +276 genotype in the model. No linkage was observed at 5p15. Our data indicate a strong genetic control of serum adiponectin. A small proportion of this can be attributed in our population to variability at the APM1 locus, but an as yet unidentified gene on 14q13 appears to play a much bigger role.

insulin resistance; adipocytokines; heritability; haplotype-tagging single-nucleotide polymorphisms; linkage study




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