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Physiol. Genomics (July 13, 2004). doi:10.1152/physiolgenomics.00122.2004
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Submitted on May 25, 2004
Accepted on July 7, 2004

MULTIGENIC CONTROL OF SERUM ADIPONECTIN LEVELS: EVIDENCE FOR A ROLE OF THE APM1 GENE AND A LOCUS ON 14q13

Claudia Menzaghi1*, Tonino Ercolino2, Lucia Salvemini1, Angelo Coco1, Sung-Hoon Kim2, Grazia Fini1, Alessandro Doria2, and Vincenzo Trischitta3

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, MA, USA
3 Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Department of Clinical Sciences, University La Sapienza, Rome, Italy

* To whom correspondence should be addressed. E-mail: c.menzaghi{at}operapadrepio.it.

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 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, non-diabetic 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 component analysis of 737 non-diabetic 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.




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