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Genetic Influences of Adiponectin on Insulin Resistance, Type 2 Diabetes, and Cardiovascular Disease
Ist Teil von
Diabetes (New York, N.Y.), 2007-05, Vol.56 (5), p.1198-1209
Ort / Verlag
Alexandria, VA: American Diabetes Association
Erscheinungsjahr
2007
Quelle
MEDLINE
Beschreibungen/Notizen
Genetic Influences of Adiponectin on Insulin Resistance, Type 2 Diabetes, and Cardiovascular Disease
Claudia Menzaghi 1 ,
Vincenzo Trischitta 1 2 and
Alessandro Doria 3
1 Research Unit of Diabetology and Endocrinology, Scientific Institute “Casa Sollievo della Sofferenza,” San Giovanni Rotondo,
Italy
2 Department of Clinical Sciences, University La Sapienza, Rome, Italy
3 Research Division, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Massachusetts
Address correspondence and reprint requests to Alessandro Doria, MD, PhD, MPH, Section on Genetics & Epidemiology, Joslin
Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail: alessandro.doria{at}joslin.harvard.edu ; or to Claudia Menzaghi, PhD, Research Unit of DiabetologyEndocrinology, Scientific Institute “Casa Sollievo della Sofferenza,”
Viale Padre Pio, 71013 San Giovanni Rotondo (FG), Italy. E-mail: c.menzaghi{at}operapadrepio.it
Abstract
Recent evidence points to molecules secreted by the adipose tissue, or adipokines, as possible links between increased adipose
mass and metabolic abnormalities. Among these molecules, adiponectin has drawn much attention because of its insulin-sensitizing
and antiatherogenic actions, suggesting that genetic deficits in its production or action may contribute to insulin resistance
and coronary artery disease (CAD). A meta-analysis of the data published to date supports this hypothesis. Two independent
effects, corresponding to the two linkage disequilibrium blocks that can be identified at the adiponectin locus, appear to
be present. In the 5′ block, the g.−11391G→A variant has a modest but significant effect on adiponectinemia, with a mean difference
between genotypes of 1.64 ng/ml (95% CI 0.88–2.41). In the 3′ block, the g.+276G→T variant is a strong determinant of insulin
resistance and CAD, with minor allele homozygotes having a lower homeostasis model assessment of insulin resistance (HOMA IR ) index (−0.36 units, 95% CI 0.24–0.47) and a lower cardiovascular risk (odds ratio 0.55, 95% CI 0.38–0.80) than carriers
of other genotypes. No consistent effect on BMI or risk of type 2 diabetes is evident. Polymorphisms in the genes coding for
the adiponectin receptors may also influence the risk of insulin resistance and CAD, but data on these genes are still too
sparse to draw firm conclusions. In summary, the studies published to date indicate that polymorphisms at the adiponectin
locus are indeed predictors of circulating adiponectin levels, insulin sensitivity, and atherosclerosis, highlighting the
pivotal role of this adipokine in the modulation of metabolism and atherogenesis.
AdipoR1, adiponectin receptor 1
AdipoR2, adiponectin receptor 2
CAD, coronary artery disease
HOMAIR, homeostasis model assessment of insulin resistance
LD, linkage disequilibrium
SNP, single nucleotide polymorphism
TZD, thiazolidinedione
UTR, untranslated region
WMD, weighted mean difference
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 15 February 2007. DOI: 10.2337/db06-0506.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted February 2, 2007.
Received April 13, 2006.
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