Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Diabetologia
Published in: Diabetologia 9/2011

01-09-2011 | Article

Associations between single-nucleotide polymorphisms (+45T>G, +276G>T, −11377C>G, −11391G>A) of adiponectin gene and type 2 diabetes mellitus: a systematic review and meta-analysis

Authors: L. Y. Han, Q. H. Wu, M. L. Jiao, Y. H. Hao, L. B. Liang, L. J. Gao, D. G. Legge, H. Quan, M. M. Zhao, N. Ning, Z. Kang, H. Sun

Published in: Diabetologia | Issue 9/2011

Login to get access

Abstract

Aims/hypothesis

The associations between adiponectin polymorphisms and type 2 diabetes have been studied widely; however, results are inconsistent.

Methods

We searched electronic literature databases and reference lists of relevant articles. A fixed or random effects model was used on the basis of heterogeneity. Sub-group and meta-regression analyses were conducted to explore the sources of heterogeneity.

Results

There were no statistically significant associations between +45T>G (rs2241766), +276G>T (rs1501299), −11391G>A (rs17300539) and type 2 diabetes risk. However, for −11377C>G (rs266729), the pooled OR (95% CI) for G vs C allele was 1.07 (1.03–1.11, p = 0.001). Subgroup analysis by study design revealed that −11377C>G (rs266729) dominant model (CG+GG vs CC, p = 0.0008) and G vs C allele (p = 0.0004) might be associated with type 2 diabetes risk in population-based case–control studies. After stratification by ethnicity, we found that −11377C>G (rs266729) dominant model (CG+GG vs CC, p = 0.004) and G vs C allele (p = 0.001) might be associated with type 2 diabetes risk in white individuals. In individuals with a family history of diabetes, the presence of −11391G>A (rs17300539) dominant model (GA+AA vs GG) and A vs G allele might be associated with increased risk of type 2 diabetes.

Conclusions/interpretation

The presence of +45T>G (rs2241766), +276G>T (rs1501299) and −11391G>A (rs17300539) do not appear to influence the development of type 2 diabetes. However, G vs C allele of −11377C>G (rs266729) might be a risk factor for type 2 diabetes.
Appendix
Available only for authorised users
Literature
1.
King H, Aubert RE, Herman WH (1998) Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 21:1414–1431PubMedCrossRef
2.
Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053PubMedCrossRef
3.
Stumvoll M, Goldstein BJ, van Haeften TW (2005) Type 2 diabetes: principles of pathogenesis and therapy. Lancet 365:1333–1346PubMedCrossRef
4.
Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556PubMedCrossRef
5.
Vionnet N, Hani EH, Dupont S et al (2000) Genomewide search for type 2 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 67:1470–1480PubMedCrossRef
6.
Kissebah AH, Sonnenberg GE, Myklebust J et al (2000) Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci USA 97:14478–14483PubMedCrossRef
7.
Yamauchi T, Kamon J, Waki H et al (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946PubMedCrossRef
8.
Scherer PE (2006) Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes 55:1537–1545PubMedCrossRef
9.
Hotta K, Funahashi T, Bodkin NL et al (2001) Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 50:1126–1133PubMedCrossRef
10.
Berg AH, Combs TP, Scherer PE (2002) ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 13:84–89PubMedCrossRef
11.
Yamauchi T, Oike Y, Kamon J et al (2002) Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice. Nat Genet 30:221–226PubMedCrossRef
12.
Hotta K, Funahashi T, Arita Y et al (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595–1599PubMedCrossRef
13.
Daimon M, Oizumi T, Saitoh T et al (2003) Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese population: the Funagata Study. Diabetes Care 26:2015–2020PubMedCrossRef
14.
Lindsay RS, Funahashi T, Hanson RL et al (2002) Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 360:57–58PubMedCrossRef
15.
Ling H, Waterworth DM, Stirnadel HA et al (2009) Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: the GEMS Study. Obesity (Silver Spring) 17:737–744CrossRef
16.
Heid IM, Henneman P, Hicks A et al (2010) Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: results of genome-wide association analyses including 4659 European individuals. Atherosclerosis 208:412–420PubMedCrossRef
17.
Richards JB, Waterworth D, O'Rahilly S et al (2009) A genome-wide association study reveals variants in ARL15 that influence adiponectin levels. PLoS Genet 5:e1000768PubMedCrossRef
18.
Jee SH, Sull JW, Lee JE et al (2010) Adiponectin concentrations: a genome-wide association study. Am J Hum Genet 87:545–552PubMedCrossRef
19.
Vasseur F, Helbecque N, Dina C et al (2002) Single-nucleotide polymorphism haplotypes in the both 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 11:2607–2614PubMedCrossRef
20.
Gonzalez-Sanchez JL, Zabena CA, Martinez-Larrad MT et al (2005) An SNP in the adiponectin gene is associated with decreased serum adiponectin levels and risk for impaired glucose tolerance. Obes Res 13:807–812PubMedCrossRef
21.
Menzaghi C, Trischitta V, Doria A (2007) Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease. Diabetes 56:1198–1209PubMedCrossRef
22.
Comuzzie AG, Funahashi T, Sonnenberg G et al (2001) The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab 86:4321–4325PubMedCrossRef
23.
Wolfs MG, Hofker MH, Wijmenga C, van Haeften TW (2009) Type 2 diabetes mellitus: new genetic insights will lead to new therapeutics. Curr Genomics 10:110–118PubMedCrossRef
24.
Gable DR, Hurel SJ, Humphries SE (2006) Adiponectin and its gene variants as risk factors for insulin resistance, the metabolic syndrome and cardiovascular disease. Atherosclerosis 188:231–244PubMedCrossRef
25.
Hara K, Boutin P, Mori Y et al (2002) Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 51:536–540PubMedCrossRef
26.
Menzaghi C, Ercolino T, Di PR et al (2002) A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 51:2306–2312PubMedCrossRef
27.
Lee YY, Lee NS, Cho YM et al (2005) Genetic association study of adiponectin polymorphisms with risk of type 2 diabetes mellitus in Korean population. Diabet Med 22:569–575PubMedCrossRef
28.
Ukkola O, Santaniemi M, Rankinen T et al (2005) Adiponectin polymorphisms, adiposity and insulin metabolism: HERITAGE family study and Oulu diabetic study. Ann Med 37:141–150PubMedCrossRef
29.
Li LL, Kang XL, Ran XJ et al (2007) Associations between 45T/G polymorphism of the adiponectin gene and plasma adiponectin levels with type 2 diabetes. Clin Exp Pharmacol Physiol 34:1287–1290PubMedCrossRef
30.
Yamaguchi S, Yamada Y, Matsuo H et al (2007) Gender differences in the association of gene polymorphisms with type 2 diabetes mellitus. Int J Mol Med 19:631–637PubMed
31.
Potapov VA, Chistiakov DA, Dubinina A, Shamkhalova MS, Shestakova MV, Nosikov VV (2008) Adiponectin and adiponectin receptor gene variants in relation to type 2 diabetes and insulin resistance-related phenotypes. Rev Diabet Stud 5:28–37PubMedCrossRef
32.
Mohammadzadeh G, Zarghami N (2009) Associations between single-nucleotide polymorphisms of the adiponectin gene, serum adiponectin levels and increased risk of type 2 diabetes mellitus in Iranian obese individuals. Scand J Clin Lab Invest 69:764–771PubMedCrossRef
33.
Sun H, Gong ZC, Yin JY et al (2008) The association of adiponectin allele 45T/G and −11377C/G polymorphisms with type 2 diabetes and rosiglitazone response in Chinese patients. Br J Clin Pharmacol 65:917–926PubMedCrossRef
34.
Wang X, Zhang S, Chen Y et al (2009) APM1 gene variants −11377C/G and 4545G/C are associated respectively with obesity and with non-obesity in Chinese type 2 diabetes. Diabetes Res Clin Pract 84:205–210PubMedCrossRef
35.
Suriyaprom K, Phonrat B, Namjuntra P, Harnroongroj T, Tungtrongchitr R (2010) The −11377C>G adiponectin gene polymorphism alters the adiponectin concentration and the susceptibility to type 2 diabetes in Thais. Int J Vitam Nutr Res 80:216–224PubMedCrossRef
36.
Populaire C, Mori Y, Dina C et al (2003) Does the −11377 promoter variant of APM1 gene contribute to the genetic risk for type 2 diabetes mellitus in Japanese families. Diabetologia 46:443–445PubMed
37.
Gu HF, Abulaiti A, Ostenson CG et al (2004) Single nucleotide polymorphisms in the proximal promoter region of the adiponectin (APM1) gene are associated with type 2 diabetes in Swedish caucasians. Diabetes 53(Suppl 1):S31–S35PubMedCrossRef
38.
Vasseur F, Helbecque N, Lobbens S et al (2005) Hypoadiponectinaemia and high risk of type 2 diabetes are associated with adiponectin-encoding (ACDC) gene promoter variants in morbid obesity: evidence for a role of ACDC in diabesity. Diabetologia 48:892–899PubMedCrossRef
39.
Yang WS, Yang YC, Chen CL et al (2007) Adiponectin SNP276 is associated with obesity, the metabolic syndrome, and diabetes in the elderly. Am J Clin Nutr 86:509–513PubMed
40.
Magdalena S, Malgorzata M, Beata W et al (2009) Variants of the adiponectin gene and type 2 diabetes in a Polish population. Acta Diabetol 46:317–322CrossRef
41.
Wang Y, Zhang D, Liu Y et al (2009) Association study of the single nucleotide polymorphisms in adiponectin-associated genes with type 2 diabetes in Han Chinese. J Genet Genomics 36:417–423PubMedCrossRef
42.
Yang M, Qiu CC, Chen W, Xu LL, Yu M, Xiang HD (2008) Identification of a regulatory single nucleotide polymorphism in the adiponectin (APM1) gene associated with type 2 diabetes in Han nationality. Biomed Environ Sci 21:454–459PubMedCrossRef
43.
Vendramini MF, Pereira AC, Ferreira SR, Kasamatsu TS, Moises RS (2010) Association of genetic variants in the adiponectin encoding gene (ADIPOQ) with type 2 diabetes in Japanese Brazilians. J Diabetes Complications 24:115–120PubMedCrossRef
44.
Gibson F, Froguel P (2004) Genetics of the APM1 locus and its contribution to type 2 diabetes susceptibility in French Caucasians. Diabetes 53:2977–2983PubMedCrossRef
45.
Hu FB, Doria A, Li T et al (2004) Genetic variation at the adiponectin locus and risk of type 2 diabetes in women. Diabetes 53:209–213PubMedCrossRef
46.
Fumeron F, Aubert R, Siddiq A et al (2004) Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study. Diabetes 53:1150–1157PubMedCrossRef
47.
de Courten BV, Hanson RL, Funahashi T et al (2005) Common polymorphisms in the adiponectin gene ACDC are not associated with diabetes in Pima Indians. Diabetes 54:284–289CrossRef
48.
Tso AW, Sham PC, Wat NM et al (2006) Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese subjects with impaired glucose tolerance: a 5-year follow-up study. Diabetologia 49:1806–1815PubMedCrossRef
49.
Nannipieri M, Posadas R, Bonotti A et al (2006) Polymorphism of the 3′-untranslated region of the leptin receptor gene, but not the adiponectin SNP45 polymorphism, predicts type 2 diabetes: a population-based study. Diabetes Care 29:2509–2511PubMedCrossRef
50.
Schwarz PE, Govindarajalu S, Towers W et al (2006) Haplotypes in the promoter region of the ADIPOQ gene are associated with increased diabetes risk in a German Caucasian population. Horm Metab Res 38:447–451PubMedCrossRef
51.
Gable DR, Matin J, Whittall R et al (2007) Common adiponectin gene variants show different effects on risk of cardiovascular disease and type 2 diabetes in European subjects. Ann Hum Genet 71:453–466PubMedCrossRef
52.
Olckers A, Towers GW, der Merwe Av, Schwarz PE, Rheeder P, Schutte AE (2007) Protective effect against type 2 diabetes mellitus identified within the ACDC gene in a black South African diabetic cohort. Metabolism 56:587–592PubMedCrossRef
53.
Jaziri R, Lobbens S, Aubert R et al (2006) The PPARG Pro12Ala polymorphism is associated with a decreased risk of developing hyperglycemia over 6 years and combines with the effect of the APM1 G-11391A single nucleotide polymorphism: the Data From an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) Study. Diabetes 55:1157–1162PubMedCrossRef
54.
Chiodini BD, Specchia C, Gori F et al (2010) Adiponectin gene polymorphisms and their effect on the risk of myocardial infarction and type 2 diabetes: an association study in an Italian population. Ther Adv Cardiovasc Dis 4:223–230PubMedCrossRef
55.
Hivert MF, Manning AK, McAteer JB et al (2008) Common variants in the adiponectin gene (ADIPOQ) associated with plasma adiponectin levels, type 2 diabetes, and diabetes-related quantitative traits: the Framingham Offspring Study. Diabetes 57:3353–3359PubMedCrossRef
56.
Staiger H, Machicao F, Fritsche A, Haring HU (2009) Pathomechanisms of type 2 diabetes genes. Endocr Rev 30:557–585PubMedCrossRef
57.
Lichtenstein MJ, Mulrow CD, Elwood PC (1987) Guidelines for reading case–control studies. J Chronic Dis 40:893–903PubMedCrossRef
58.
Thakkinstian A, McEvoy M, Minelli C et al (2005) Systematic review and meta-analysis of the association between β2-adrenoceptor polymorphisms and asthma: a HuGE review. Am J Epidemiol 162:201–211PubMedCrossRef
59.
Attia J, Thakkinstian A, D’Este C (2003) Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol 56:297–303PubMedCrossRef
60.
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558PubMedCrossRef
61.
62.
Morgan JF (2007) p Value fetishism and use of the Bonferroni adjustment. Evid Based Ment Health 10:34–35PubMedCrossRef
63.
Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMed
64.
Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56:455–463PubMedCrossRef
65.
Voight BF, Scott LJ, Steinthorsdottir V et al (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 42:579–589PubMedCrossRef
66.
Gong M, Long J, Liu Q, Deng HC (2010) Association of the ADIPOQ rs17360539 and rs266729 polymorphisms with type 2 diabetes: a meta-analysis. Mol Cell Endocrinol 325:78–83PubMedCrossRef
67.
Stumvoll M, Tschritter O, Fritsche A et al (2002) Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes 51:37–41PubMedCrossRef
68.
Stenvinkel P, Marchlewska A, Pecoits-Filho R et al (2004) Adiponectin in renal disease: relationship to phenotype and genetic variation in the gene encoding adiponectin. Kidney Int 65:274–281PubMedCrossRef
69.
Li S, Li L, Li K et al (2008) Association of adipose most abundant transcript 1 gene (apM1) with type 2 diabetes mellitus in a Chinese population: a meta-analysis of case–control studies. Clin Endocrinol (Oxf) 68:885–889CrossRef
70.
Zeggini E, Ioannidis JP (2009) Meta-analysis in genome-wide association studies. Pharmacogenomics 10:191–201PubMedCrossRef
71.
Matsuzawa Y (2005) Adiponectin: identification, physiology and clinical relevance in metabolic and vascular disease. Atheroscler Suppl 6:7–14PubMedCrossRef
72.
Koerner A, Kratzsch J, Kiess W (2005) Adipocytokines: leptin—the classical, resistin—the controversical, adiponectin—the promising, and more to come. Best Pract Res Clin Endocrinol Metab 19:525–546PubMedCrossRef
Metadata
Title
Associations between single-nucleotide polymorphisms (+45T>G, +276G>T, −11377C>G, −11391G>A) of adiponectin gene and type 2 diabetes mellitus: a systematic review and meta-analysis
Authors
L. Y. Han
Q. H. Wu
M. L. Jiao
Y. H. Hao
L. B. Liang
L. J. Gao
D. G. Legge
H. Quan
M. M. Zhao
N. Ning
Z. Kang
H. Sun
Publication date
01-09-2011
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 9/2011
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-011-2202-9

Other articles of this Issue 9/2011

Diabetologia 9/2011 Go to the issue

Short Communication

Quantitative EEG in type 1 diabetic adults with childhood exposure to severe hypoglycaemia: a 16 year follow-up study

Article

Glycated albumin but not HbA1c reflects glycaemic control in patients with neonatal diabetes mellitus

Commentary

Insulitis in the human endocrine pancreas: Does a viral infection lead to inflammation and beta cell replication?

Article

Role for inducible cAMP early repressor in promoting pancreatic beta cell dysfunction evoked by oxidative stress in human and rat islets

Erratum

Erratum to: Dynamic evaluation of renal resistive index in normoalbuminuric patients with newly diagnosed hypertension or type 2 diabetes

Article

Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits