Volume 21, Issue 7 pp. 776-781

The adiponectin gene SNP+45 is associated with coronary artery disease in Type 2 (non-insulin-dependent) diabetes mellitus

C. Lacquemant,

C. Lacquemant

Genomics Medicine Department and the Hammersmith Genome Centre, Imperial College, London, UK,

Search for more papers by this author

P. Froguel,

Corresponding Author

P. Froguel

Genomics Medicine Department and the Hammersmith Genome Centre, Imperial College, London, UK,

Institute of Biology-CNRS 8090, Pasteur Institute, Lille, France and

Correspondence to: Pr. Philippe Froguel, Genomic Medicine and the Hammersmith Genome Centre, Imperial College, Hammersmith Hospital, Cane Road, London, W12 0NN, UK. E-mail: [email protected]Search for more papers by this author

S. Lobbens,

S. Lobbens

Institute of Biology-CNRS 8090, Pasteur Institute, Lille, France and

Search for more papers by this author

P. Izzo,

P. Izzo

Division of Endocrinology, Lausanne University Hospital, Switzerland

Search for more papers by this author

C. Dina,

C. Dina

Institute of Biology-CNRS 8090, Pasteur Institute, Lille, France and

Search for more papers by this author

J. Ruiz,

J. Ruiz

Institute of Biology-CNRS 8090, Pasteur Institute, Lille, France and

Division of Endocrinology, Lausanne University Hospital, Switzerland

Search for more papers by this author

C. Lacquemant,

C. Lacquemant

Genomics Medicine Department and the Hammersmith Genome Centre, Imperial College, London, UK,

Search for more papers by this author

P. Froguel,

Corresponding Author

P. Froguel

Genomics Medicine Department and the Hammersmith Genome Centre, Imperial College, London, UK,

Institute of Biology-CNRS 8090, Pasteur Institute, Lille, France and

S. Lobbens,

S. Lobbens

Institute of Biology-CNRS 8090, Pasteur Institute, Lille, France and

Search for more papers by this author

P. Izzo,

P. Izzo

Division of Endocrinology, Lausanne University Hospital, Switzerland

Search for more papers by this author

C. Dina,

C. Dina

Institute of Biology-CNRS 8090, Pasteur Institute, Lille, France and

Search for more papers by this author

J. Ruiz,

J. Ruiz

Institute of Biology-CNRS 8090, Pasteur Institute, Lille, France and

Division of Endocrinology, Lausanne University Hospital, Switzerland

Search for more papers by this author

First published: 21 June 2004

https://doi.org/10.1111/j.1464-5491.2004.01224.x

Citations: 79

Share a link

Email
Wechat
Bluesky

Abstract

Background The ACRP30/adiponectin gene on chromosome 3q27, a region linked to the metabolic syndrome, encodes for the abundant adipocyte-specific secreted protein. Consistent rodent and human studies suggested that this adipokine may be a molecular link between metabolic and cardiovascular diseases.

Aims In order to investigate the role of single nucleotide polymorphisms (SNPs) within the APM1 gene in the susceptibility to coronary artery disease (CAD), we performed a case-control study on Caucasian Type 2 (non-insulin-dependent) diabetic patients, a population at high-risk for CAD.

Methods Five APM1 SNPs were genotyped in 162 Type 2 diabetic French and Swiss subjects with CAD and in 315 Type 2 diabetic French and Swiss subjects without CAD.

Results In univariate analysis, SNP+45 T>G was associated with CAD (OR 1.9 95% CI 1.2–2.9 P = 0.0036). In multivariate analysis, SNP+45 T>G remained associated with CAD (OR 1.2 95% CI 0.8–1.9 P = 0.017), independently of classical cardiovascular risk factors including components of the metabolic syndrome. SNP haplotype analyses revealed a CAD protective combination of all SNP wild-type alleles (OR 0.5 95% CI 0.3–0.7 P = 0.0006).

Conclusions Our study, performed in diabetic subjects, revealed an association between individual SNP+45 in the APM1 gene and CAD. Furthermore, the susceptibility for CAD due to SNP+45 was independent of classic cardiovascular risk factors. Further studies will be necessary to confirm the role of SNP+45 in the development of CAD. However, ACRP30/adiponectin may contribute to atherosclerosis susceptibility in high-risk populations such as Type 2 diabetic subjects.

References

1 Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595–1607.
10.2337/diab.37.12.1595
CAS PubMed Web of Science® Google Scholar
2 Ruiz J, Blanche H, Cohen N, Velho G, Cambien F, Cohen D et al. Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci USA 1994; 91: 3662–3665.
10.1073/pnas.91.9.3662
CAS PubMed Web of Science® Google Scholar
3 Ruiz J, Blanche H, James RW, Garin MC, Vaisse C, Charpentier G et al. Gln-Arg192 polymorphism of paraoxonase and coronary heart disease in type diabetes. Lancet 1995; 346: 869–872.
10.1016/S0140-6736(95)92709-3
CAS PubMed Web of Science® Google Scholar
4 Vionnet N, Hani EH, Dupont S, Gallina S, Francke S, Dotte S et al. Genomewide search for type diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21-q24. Am J Hum Genet 2000; 67: 1470–1480.
10.1086/316887
CAS PubMed Web of Science® Google Scholar
5 Kissebah AH, Sonnenberg GE, Myklebust J, Goldstein M, Broman K, James RG et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci USA 2000; 97: 14478–14483.
10.1073/pnas.97.26.14478
CAS PubMed Web of Science® Google Scholar
6 Francke S, Manraj M, Lacquemant C, Lecoeur C, Lepretre F, Passa P et al. A genome wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27. Hum Mol Genet 2001; 10: 2751–2765.
10.1093/hmg/10.24.2751
CAS PubMed Web of Science® Google Scholar
7 Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (adipose most abundant gene transcript 1). Biochem Biophys Res Commun 1996; 221: 286–289.
10.1006/bbrc.1996.0587
CAS PubMed Web of Science® Google Scholar
8 Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K et al. Genetic variation in the gene encoding adiponectin is associated with increased risk of type 2 diabetes in the Japanese population. Diabetes 2002; 51: 536–540.
10.2337/diabetes.51.2.536
CAS PubMed Web of Science® Google Scholar
9 Stumvoll M, Tschritter O, Fritsche A, Staiger H, Renn W, Weisser M et al. Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes 2002; 51: 37–41.
10.2337/diabetes.51.1.37
CAS PubMed Web of Science® Google Scholar
10 Menzaghi C, Ercolino T, Di Paola R, Berg AH, Warram JH, Scherer PE et al. A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 2002; 51: 2306–2312.
10.2337/diabetes.51.7.2306
CAS PubMed Web of Science® Google Scholar
11 Vasseur F, Helbecque N, Dina C, Lobbens S, Delannoy V, Gaget S et al. Single-nucleotide polymorphism haplotypes in both the proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet 2002; 11: 2607–2614.
10.1093/hmg/11.21.2607
CAS PubMed Web of Science® Google Scholar
12 Populaire C, Mori Y, Dina C, Vasseur F, Vaxillaire M, Kadowaki T et al. Does the −11377 promoter variant of APM1 gene contribute to the genetic risk for Type 2 diabetes mellitus in Japanese families?. Diabetologia 2003; 46: 443–445.
10.1007/s00125-003-1050-7
CAS PubMed Web of Science® Google Scholar
13 Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001; 98: 2005–10.
10.1073/pnas.98.4.2005
CAS PubMed Web of Science® Google Scholar
14 Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Medicine 2001; 7: 941–946.
10.1038/90984
CAS PubMed Web of Science® Google Scholar
15 Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257: 79–83.
10.1006/bbrc.1999.0255
CAS PubMed Web of Science® Google Scholar
16 Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000; 20: 1595–1599.
10.1161/01.ATV.20.6.1595
CAS PubMed Web of Science® Google Scholar
17 Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930–35.
10.1210/jcem.86.5.7463
CAS PubMed Web of Science® Google Scholar
18 Comuzzie AG, Funahashi T, Sonnenberg G, Martin LJ, Jacob HJ, Black AE et al. The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab 2001; 86: 4321–4325.
10.1210/jcem.86.9.7878
CAS PubMed Web of Science® Google Scholar
19 Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001; 103: 1057–1063.
10.1161/01.CIR.103.8.1057
CAS PubMed Web of Science® Google Scholar
20 Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-κB signaling through a cAMP-dependent pathway. Circulation 2000; 102: 1296–1301.
10.1161/01.CIR.102.11.1296
CAS PubMed Web of Science® Google Scholar
21 Mantel N, Haenzsel W. Statistical aspects of the analysis of data from retrospective studies of the disease. J Natl Cancer Inst 1959; 22: 719–748.
CAS PubMed Web of Science® Google Scholar
22 Terwilliger JD, Ott J. Handbook of Human Genetic Linkage. Baltimore and London: The Johns Hopkins University Press, 1994.
Google Scholar
23 Sham PC, Curtis D. Monte Carlo tests for associations between disease and alleles at highly polymorphic loci. Ann Hum Genet 1995; 59: 97–105.
10.1111/j.1469-1809.1995.tb01608.x
CAS PubMed Web of Science® Google Scholar
24 Cartegni L, Chew SL, Krainer AR. Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat Rev Genet 2002; 3: 285–298.
10.1038/nrg775
CAS PubMed Web of Science® Google Scholar
25 Yang WS, Tsou PL, Lee WJ, Tseng DL, Chen CL, Peng CC et al. Allele-specific differential expression of a common adiponectin gene polymorphism related to obesity. J Mol Med 2003; 81: 428–434.
10.1007/s00109-002-0409-4
CAS PubMed Web of Science® Google Scholar
26 Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 2002; 277: 25863–25866.
10.1074/jbc.C200251200
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume21, Issue7

July 2004

Pages 776-781

The adiponectin gene SNP+45 is associated with coronary artery disease in Type 2 (non-insulin-dependent) diabetes mellitus

Abstract

References

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

The adiponectin gene SNP+45 is associated with coronary artery disease in Type 2 (non-insulin-dependent) diabetes mellitus

Abstract

References

Citing Literature

References

Related

Information