Common adiponectin gene variants show different effects on risk of cardiovascular disease and type 2 diabetes in European subjects

D. R. Gable, J. Matin, R. Whittall, H. Cakmak, Ka Wah Li, J. Cooper, G. J. Miller, Steve E. Humphries, Anders Hamsten, Irène Juhan-Vague, Maurizio Margaglione, Giovanni di Minno, John Yudkin, Elena Tremoli

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Alterations in the secretion of adipokines may explain the link between obesity, type 2 diabetes (T2DM) and coronary artery disease (CAD). These conditions have been associated with variation in the adiponectin gene, although evidence for this relationship has been variable, with differences found even in similar samples. This study aims to clarify these inconsistencies by determining the impact of identified adiponectin gene (ADIPOQ) variants (-11391G>A,-1377C>G[promoter] and +45T>G[exon 2]and +276G>T[intron 2]) on the prospective risk of CAD and T2DM in healthy men, and on adverse metabolic markers, in myocardial infarct survivors and controls from different parts of Europe. The hazard ratio for cardiovascular disease varied across the -11391GG/GA/AA(p = 0.03) and -11371CC/CG/GG(p = 0.05) genotypes only. In contrast, only the +45T>G variant (3.80[1.76-8.24]) was associated with T2DM, while two haplotypes GCTT/GCGG (p <0.05) and +276G>T(p = 0.01) increased risk in interaction with obesity. The variants were associated with a number of biomarkers in Southern but not Northern Europe (p = 0.01), despite no significant differences in allele or haplotype frequencies (p > 0.44). A risk haplotype could not be identified in either sample. Adiponectin gene variants are hence currently poor markers for the development of T2DM and CAD. Their influence on risk depends significantly on interactions that are not currently understood with either genetic variation elsewhere or the environment of the sample studied.

Original languageEnglish
Pages (from-to)453-466
Number of pages14
JournalAnnals of Human Genetics
Volume71
Issue number4
DOIs
Publication statusPublished - Jul 2007

Fingerprint

Adiponectin
Type 2 Diabetes Mellitus
Cardiovascular Diseases
Haplotypes
Coronary Artery Disease
Genes
Obesity
Adipokines
Introns
Survivors
Exons
Biomarkers
Alleles
Myocardial Infarction
Genotype

Keywords

  • Adiponectin
  • Cardiovascular disease
  • Metabolic Syndrome
  • Obesity

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Common adiponectin gene variants show different effects on risk of cardiovascular disease and type 2 diabetes in European subjects. / Gable, D. R.; Matin, J.; Whittall, R.; Cakmak, H.; Li, Ka Wah; Cooper, J.; Miller, G. J.; Humphries, Steve E.; Hamsten, Anders; Juhan-Vague, Irène; Margaglione, Maurizio; di Minno, Giovanni; Yudkin, John; Tremoli, Elena.

In: Annals of Human Genetics, Vol. 71, No. 4, 07.2007, p. 453-466.

Research output: Contribution to journalArticle

Gable, DR, Matin, J, Whittall, R, Cakmak, H, Li, KW, Cooper, J, Miller, GJ, Humphries, SE, Hamsten, A, Juhan-Vague, I, Margaglione, M, di Minno, G, Yudkin, J & Tremoli, E 2007, 'Common adiponectin gene variants show different effects on risk of cardiovascular disease and type 2 diabetes in European subjects', Annals of Human Genetics, vol. 71, no. 4, pp. 453-466. https://doi.org/10.1111/j.1469-1809.2006.00340.x
Gable, D. R. ; Matin, J. ; Whittall, R. ; Cakmak, H. ; Li, Ka Wah ; Cooper, J. ; Miller, G. J. ; Humphries, Steve E. ; Hamsten, Anders ; Juhan-Vague, Irène ; Margaglione, Maurizio ; di Minno, Giovanni ; Yudkin, John ; Tremoli, Elena. / Common adiponectin gene variants show different effects on risk of cardiovascular disease and type 2 diabetes in European subjects. In: Annals of Human Genetics. 2007 ; Vol. 71, No. 4. pp. 453-466.
@article{ccf49fac88134b3fa49d396150fa4e1d,
title = "Common adiponectin gene variants show different effects on risk of cardiovascular disease and type 2 diabetes in European subjects",
abstract = "Alterations in the secretion of adipokines may explain the link between obesity, type 2 diabetes (T2DM) and coronary artery disease (CAD). These conditions have been associated with variation in the adiponectin gene, although evidence for this relationship has been variable, with differences found even in similar samples. This study aims to clarify these inconsistencies by determining the impact of identified adiponectin gene (ADIPOQ) variants (-11391G>A,-1377C>G[promoter] and +45T>G[exon 2]and +276G>T[intron 2]) on the prospective risk of CAD and T2DM in healthy men, and on adverse metabolic markers, in myocardial infarct survivors and controls from different parts of Europe. The hazard ratio for cardiovascular disease varied across the -11391GG/GA/AA(p = 0.03) and -11371CC/CG/GG(p = 0.05) genotypes only. In contrast, only the +45T>G variant (3.80[1.76-8.24]) was associated with T2DM, while two haplotypes GCTT/GCGG (p <0.05) and +276G>T(p = 0.01) increased risk in interaction with obesity. The variants were associated with a number of biomarkers in Southern but not Northern Europe (p = 0.01), despite no significant differences in allele or haplotype frequencies (p > 0.44). A risk haplotype could not be identified in either sample. Adiponectin gene variants are hence currently poor markers for the development of T2DM and CAD. Their influence on risk depends significantly on interactions that are not currently understood with either genetic variation elsewhere or the environment of the sample studied.",
keywords = "Adiponectin, Cardiovascular disease, Metabolic Syndrome, Obesity",
author = "Gable, {D. R.} and J. Matin and R. Whittall and H. Cakmak and Li, {Ka Wah} and J. Cooper and Miller, {G. J.} and Humphries, {Steve E.} and Anders Hamsten and Ir{\`e}ne Juhan-Vague and Maurizio Margaglione and {di Minno}, Giovanni and John Yudkin and Elena Tremoli",
year = "2007",
month = "7",
doi = "10.1111/j.1469-1809.2006.00340.x",
language = "English",
volume = "71",
pages = "453--466",
journal = "Annals of Human Genetics",
issn = "0003-4800",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Common adiponectin gene variants show different effects on risk of cardiovascular disease and type 2 diabetes in European subjects

AU - Gable, D. R.

AU - Matin, J.

AU - Whittall, R.

AU - Cakmak, H.

AU - Li, Ka Wah

AU - Cooper, J.

AU - Miller, G. J.

AU - Humphries, Steve E.

AU - Hamsten, Anders

AU - Juhan-Vague, Irène

AU - Margaglione, Maurizio

AU - di Minno, Giovanni

AU - Yudkin, John

AU - Tremoli, Elena

PY - 2007/7

Y1 - 2007/7

N2 - Alterations in the secretion of adipokines may explain the link between obesity, type 2 diabetes (T2DM) and coronary artery disease (CAD). These conditions have been associated with variation in the adiponectin gene, although evidence for this relationship has been variable, with differences found even in similar samples. This study aims to clarify these inconsistencies by determining the impact of identified adiponectin gene (ADIPOQ) variants (-11391G>A,-1377C>G[promoter] and +45T>G[exon 2]and +276G>T[intron 2]) on the prospective risk of CAD and T2DM in healthy men, and on adverse metabolic markers, in myocardial infarct survivors and controls from different parts of Europe. The hazard ratio for cardiovascular disease varied across the -11391GG/GA/AA(p = 0.03) and -11371CC/CG/GG(p = 0.05) genotypes only. In contrast, only the +45T>G variant (3.80[1.76-8.24]) was associated with T2DM, while two haplotypes GCTT/GCGG (p <0.05) and +276G>T(p = 0.01) increased risk in interaction with obesity. The variants were associated with a number of biomarkers in Southern but not Northern Europe (p = 0.01), despite no significant differences in allele or haplotype frequencies (p > 0.44). A risk haplotype could not be identified in either sample. Adiponectin gene variants are hence currently poor markers for the development of T2DM and CAD. Their influence on risk depends significantly on interactions that are not currently understood with either genetic variation elsewhere or the environment of the sample studied.

AB - Alterations in the secretion of adipokines may explain the link between obesity, type 2 diabetes (T2DM) and coronary artery disease (CAD). These conditions have been associated with variation in the adiponectin gene, although evidence for this relationship has been variable, with differences found even in similar samples. This study aims to clarify these inconsistencies by determining the impact of identified adiponectin gene (ADIPOQ) variants (-11391G>A,-1377C>G[promoter] and +45T>G[exon 2]and +276G>T[intron 2]) on the prospective risk of CAD and T2DM in healthy men, and on adverse metabolic markers, in myocardial infarct survivors and controls from different parts of Europe. The hazard ratio for cardiovascular disease varied across the -11391GG/GA/AA(p = 0.03) and -11371CC/CG/GG(p = 0.05) genotypes only. In contrast, only the +45T>G variant (3.80[1.76-8.24]) was associated with T2DM, while two haplotypes GCTT/GCGG (p <0.05) and +276G>T(p = 0.01) increased risk in interaction with obesity. The variants were associated with a number of biomarkers in Southern but not Northern Europe (p = 0.01), despite no significant differences in allele or haplotype frequencies (p > 0.44). A risk haplotype could not be identified in either sample. Adiponectin gene variants are hence currently poor markers for the development of T2DM and CAD. Their influence on risk depends significantly on interactions that are not currently understood with either genetic variation elsewhere or the environment of the sample studied.

KW - Adiponectin

KW - Cardiovascular disease

KW - Metabolic Syndrome

KW - Obesity

UR - http://www.scopus.com/inward/record.url?scp=33947583511&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947583511&partnerID=8YFLogxK

U2 - 10.1111/j.1469-1809.2006.00340.x

DO - 10.1111/j.1469-1809.2006.00340.x

M3 - Article

VL - 71

SP - 453

EP - 466

JO - Annals of Human Genetics

JF - Annals of Human Genetics

SN - 0003-4800

IS - 4

ER -