Association of ADIPOR2 gene variants with cardiovascular disease and type 2 diabetes risk in individuals with impaired glucose tolerance: the Finnish Diabetes Prevention Study

Cardiovascular Diabetology

Original Investigation

Niina Siitonen¹  Leena Pulkkinen¹  Marjukka Kolehmainen¹  Ursula Schwab²  Matti Uusitupa³  Jaana Lindström⁴  Jaakko Tuomilehto⁵  Johan G Eriksson⁶  Pirjo Ilanne-Parikka⁷  Sirkka Keinänen-Kiukaanniemi⁸ 

[1] Department of Clinical Nutrition and Food and Health Research Centre, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland;Department of Clinical Nutrition and Food and Health Research Centre, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland;Institute of Medicine, Clinical Medicine, Kuopio University Hospital, Kuopio, Finland;Department of Clinical Nutrition and Food and Health Research Centre, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland;Research Unit, Kuopio University Hospital, Kuopio, Finland;Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland;Department of Public Health, University of Helsinki, Helsinki, Finland;Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland;Department of Public Health, University of Helsinki, Helsinki, Finland;South Ostrobothnia Central Hospital, Seinäjoki, Finland;Department of Preventive and Clinical Medicine, Danube-Universität Krems, Krems, Austria;Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland;Folkhalsan Research Centre, Helsinki, Finland;Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland;Vasa Central Hospital, Vasa, Finland;Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland;Diabetes Centre, Finnish Diabetes Association, Tampere, Finland;Science Centre, Pirkanmaa Hospital District, Tampere University Hospital, Tampere, Finland;Institute of Health Sciences, University of Oulu, Oulu, Finland;Unit of General Practice, Oulu University Hospital, Oulu, Finland;Health Centre of Oulu, Oulu Finland;

关键词: Adiponectin;    adiponectin receptor 2;    gene;    single nucleotide polymorphism;    cardiovascular disease;    type 2 diabetes;   

DOI  :  10.1186/1475-2840-10-83

 received in 2011-07-10, accepted in 2011-09-24,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundAdiponectin is an adipokine with insulin-sensitising and anti-atherogenic effects. Two receptors for adiponectin, ADIPOR1 and ADIPOR2, have been characterized that mediate effects of adiponectin in various tissues. We examined whether genetic variation in ADIPOR2 predicts the development of cardiovascular disease (CVD) and/or Type 2 Diabetes (T2DM) in individuals with impaired glucose tolerance (IGT) participating the Finnish Diabetes Prevention Study (DPS).MethodsCVD morbidity and mortality data were collected during a median follow-up of 10.2 years (range 1-13 years) and conversion from IGT to T2DM was assessed during a median follow-up of 7 years (range 1-11 years). Altogether eight SNPs in the ADIPOR2 locus were genotyped in 484 participants of the DPS. Moreover, the same SNPs were genotyped and the mRNA expression levels of ADIPOR2 were determined in peripheral blood mononuclear cells and subcutaneous adipose tissue samples derived from 56 individuals participating in the Genobin study.ResultsIn the DPS population, four SNPs (rs10848554, rs11061937, rs1058322, rs16928751) were associated with CVD risk, and two remained significant (p = 0.014 for rs11061937 and p = 0.020 for rs1058322) when all four were included in the same multi-SNP model. Furthermore, the individuals homozygous for the rare minor alleles of rs11061946 and rs11061973 had increased risk of converting from IGT to T2DM. Allele-specific differences in the mRNA expression levels for the rs1058322 variant were seen in peripheral blood mononuclear cells derived from participants of the Genobin study.ConclusionsOur results suggest that SNPs in the ADIPOR2 may modify the risk of CVD in individuals with IGT, possibly through alterations in the mRNA expression levels. In addition an independent genetic signal in ADIPOR2 locus may have an impact on the risk of developing T2DM in individuals with IGT.Trial registration numberClinicalTrials.gov NCT00518167

【 授权许可】

CC BY   
© Siitonen et al; licensee BioMed Central Ltd. 2011