Abstract
Patients with type 2 diabetes (T2D) are more susceptible to develop cardiovascular complications than non-diabetic subjects. Several studies have indicated a role of adiponectin gene in the increased coronary artery disease (CAD) risk in T2D patients. The data however is limited and have been inconsistent. In this study we examined the association of SNP45T>G and SNP276G>T of adiponectin gene with CAD risk in T2D patients in a Saudi population. A total of 418 type 2 diabetic patients were randomly recruited in this study from the RIYADH COHORT. Of the total diabetes patients, 123 were also diagnosed to have CAD, while the rest were control subjects. Anthropometric, clinical and biochemical parameters were measured by standard procedures. Genotyping of polymorphisms was carried out by PCR–RFLP analysis. Genotype distribution of SNP45T>G was significantly (P = 0.005) different between control and CAD subjects, while the distribution of SNP276G>T genotypes was comparable between the subjects. The SNP45T>G was significantly associated with risk of CAD [OR (95% CI), 4.7 (1.6–13.5), P < 0.003] but not SNP276G>T [OR (95% CI), 1.02 (0.53–1.9), P > 0.05]. The association of SNP45T>G with CAD risk remained significant even after adjusting for potential confounding factors [OR (95% CI), 7.2 (1.1–45.9), P < 0.05]. The SNP45T>G of adiponectin gene is an independent risk factor for CAD in T2D patients in a Saudi population. These findings support a role for adiponectin gene in the increased CAD risk in diabetes patients and are consistent with genetic heterogeneity in the association between adiponectin gene and coronary artery disease.
Similar content being viewed by others
References
Ferrarezi DA, Cheurfa N, Reis AF, Fumeron F, Velho G (2007) Adiponectin gene and cardiovascular risk in type 2 diabetic patients: a review of evidences. Arq Bras Endocrinol Metab 51:153–159
Mantzoros CS, Li T, Manson JE, Meigs JB, Hu FB (2005) Circulating adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in women with type 2 diabetes. J Clin Endocrinol Metab 90:4542–4548
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 188:231–244
Han SH, Quon MJ, Kim JA, Koh KK (2007) Adiponectin and cardiovascular disease: response to therapeutic interventions. J Am Coll Cardiol 49:531–538
Kawano J, Arora R (2009) The role of adiponectin in obesity, diabetes, and cardiovascular disease. J Cardiometab Syndr 4:44–49
Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K (1996) cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (adipose most abundant gene transcript 1). Biochem Biophys Res Commun 221:286–289
Mori Y, Otabe S, Dina C et al (2002) Genome-wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate Loci on 7p and 11p. Diabetes 51:1247–1255
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 67:1470–1480
Francke S, Manraj M, Lacquemant C et al (2001) 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 10:2751–2765
Kissebah AH, Sonnenberg GE, Myklebust J (2000) Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci USA 97:14478–14483
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 86:4321–4325
Heid IM, Wagner SA, Gohlke H et al (2006) Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians. Diabetes 55:375–384
Menzaghi C, Trischitta V, Doria A (2007) Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease. Diabetes 56:1198–1209
Bacci S, Menzaghi C, Ercolino T (2004) The +276 G/T single nucleotide polymorphism of the adiponectin gene is associated with coronary artery disease in type 2 diabetic patients. Diabetes Care 27:2015–2020
Qi L, Li T, Rimm E, Zhang C, Rifai N, Hunter D, Doria A, Hu FB (2005) The +276 polymorphism of the APM1 gene, plasma adiponectin concentration, and cardiovascular risk in diabetic men. Diabetes 54:1607–1610
Lacquemant C, Froguel P, Lobbens S, Izzo P, Dina C, Ruiz J (2004) The adiponectin gene SNP +45 is associated with coronary artery disease in Type 2 (non-insulin-dependent) diabetes mellitus. Diabet Med 21:776–781
Kim SH, Kang ES, Hur KY et al (2008) Adiponectin gene polymorphism 45T>G is associated with carotid artery plaques in patients with type 2 diabetes mellitus. Metabolism 57:274–279
Qi L, Doria A, Manson JE, Meigs JB, Hunter D, Mantzoros CS, Hu FB (2006) Adiponectin genetic variability, plasma adiponectin, and cardiovascular risk in patients with type 2 diabetes. Diabetes 55:1512–1516
Filippi E, Sentinelli F, Romeo S et al (2005) The adiponectin gene SNP + 276G>T associates with early-onset coronary artery disease and with lower levels of adiponectin in younger coronary artery disease patients. J Mol Med 83:711–719
Yang WS, Chuang LM (2006) Human genetics of adiponectin in the metabolic syndrome. J Mol Med 84:112–121
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 34:1287–1290
Pischon T, Pai JK, Manson JE, Hu FB, Rexrode KM, Hunter D, Rimm EB (2007) Single nucleotide polymorphisms at the adiponectin locus and risk of coronary heart disease in men and women. Obesity (Silver Spring) 15:2051–2060
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 2005 22:569–575
Hoefle G, Muendlein A, Saely CH (2007) The −11377 C>G promoter variant of the adiponectin gene, prevalence of coronary atherosclerosis, and incidence of vascular events in men. Thromb Haemost 97:451–457
Mackevics V, Heid IM, Wagner SA et al (2006) The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy Caucasians. Eur J Hum Genet 14:349–356
Yang WS, Tsou PL, Lee WJ et al (2003) Allele-specific differential expression of a common adiponectin gene polymorphism related to obesity. J Mol Med 81:428–434
Takahashi M, Arita Y, Yamagata K et al (2000) Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes Relat Metab Disord 24:861–868
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 11:2607–2614
Lindsay RS, Funahashi T, Krakoff J et al (2003) Genome-wide linkage analysis of serum adiponectin in the Pima Indian population. Diabetes 52:2419–2425
Conne B, Stutz A, Vassalli JD (2000) The 3′ untranslated region of messenger RNA: a molecular ‘hotspot’ for pathology? Nat Med 6:637–641
Cartegni L, Chew SL, Krainer AR (2002) Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat Rev Genet 3:285–298
Acknowledgments
We acknowledge the technical assistance of Mr. Abdul Khader, Mr. Usamah, and Mr. Ahmed Bamakhramah. We also acknowledge the help of Mr. Benjamin Vinodson for statistical analysis. This work was funded by a grant (Bio/2009/07) from the Research Center, College of Science, King Saud University, Riyadh, Saudi Arabia.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Al-Daghri, N.M., Al-Attas, O.S., Alokail, M.S. et al. Adiponectin gene variants and the risk of coronary artery disease in patients with type 2 diabetes. Mol Biol Rep 38, 3703–3708 (2011). https://doi.org/10.1007/s11033-010-0484-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-010-0484-5