Dear Editor,
The recent article by Mohammadzadeh et al.[1] on the latest issue of this Journal showed that the T allele +276G/T SNP of ADIPOQ gene is more associated with the increasing risk of coronary artery disease (CAD) in subjects with type 2 diabetes. Adipocytes were described in myocardial tissue of CAD patients and their role recently discussed[2,3]. Susceptibility to CAD by polymorphism in the Q gene of adiponectin has been reported for 3’-UTR, which harbours some genetic loci associated with metabolic risks and atherosclerosis[4]. Actually, previous studies have shown that the haplotype SNP +276G>T was associated with a decreased risk of CAD, after adjustment for potential confounding factors, therefore some controversial opinion still exists[5]. This evidence should be associated with the role exerted by adipocytes and adiponectin in heart physiology. In particular, in hypertensive disorder complicating pregnancy (HDCP), by investigating the population frequency of alleles, genotypes, and haplotypes of two single nucleotide polymorphisms (SNPs), namely +45T>G (rs2241766) and +276G>T (rs1501299), some authors found that the SNP +276 TT genotype was significantly associated with protection against HDCP, when compared to the pooled G genotypes[6]. Moreover, the same +276G/T SNP haplotype was strongly associated with biliary atresia, an intractable neonatal inflammatory and obliterative cholangiopathy, leading to progressive fibrosis and cirrhosis[7]. CAD is closely related to adiponectin biology. The same isoforms of adiponectin seem to be not associated to CAD severity but to glucose metabolism and its impairment[8]. In the paper by Mohammadzadeh et al.[1], T allele in +276G/T SNP haplotype is highly associated with CAD in subjects with type 2 diabetes, but this linkage should be reappraised if related much more to diabetes rather than CAD. Association of T allele in the indicated SNP with CAD may be an indirect consequence of type 2 diabetes, as reported by others[9] or a direct marker for CAD affected patients[10]. The paper by Mohammadzadeh et al.[1] assesses data coming elsewhere from literature but raises important concerns about the suitability of ADIPOQ SNPs in diagnosing susceptibility to CAD and the relationship with plasma adiponectin level. In normal, non diabetic, normoglycemic subject, this relationship does not seem to work. Therefore the question is how much predictive this SNP haplotype may be to foresee metabolic syndrome and CAD onset risk in young health subjects? Maybe, the role of adiponectin in cardiovascular physiology depends on its ability to target adiponectin receptors and to negatively regulate obesity. Some authors reported in healthy volunteers an absence of correlation between circulating adiponectin levels and biochemical markers, particularly lipoproteins and suggested that SNP +276G>T was related to an independent effect on adiponectin levels and on lipoprotein metabolism[11]. On the contrary, adiponectin genetic variants and SNP +276G>T was associated with increasing susceptibility of type 2 diabetes and plasma glucose impairment[12].
The interesting study by Mohammadzadeh et al.[1] suggests that SNP of ADIPOQ +276G>T should be related to susceptibility to glucose metabolism, while indirectly to lipid metabolism and fat-related cardiovascular damage.
Footnotes
CONFLICT OF INTEREST. None declared.
REFERENCE
- 1.Mohammadzadeh G, Ghaffari MA, Heibar H, Bazyar M. Association of two common single nucleotide polymorphisms (+45T/G and +276G/T) of ADIPOQ gene on coronary artery disease in type 2 diabetic patients. Iranian biomedical journal. 2016;20(3):152–160. doi: 10.7508/ibj.2016.03.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Mazzali G, Fantin F, Zoico E, Sepe A, Bambace C, Faccioli S, Pedrotti M, Corzato F, Rizzatti V, Faggian G, Micciolo R, Cinti S, Santini F, Zamboni M. Heart fat infiltration in subjects with and without coronary artery disease. The journal of Clinical endocrinology Metabolism. 2015;100(9):3364–3371. doi: 10.1210/jc.2015-1787. [DOI] [PubMed] [Google Scholar]
- 3.Chirumbolo S. Commentary:Heart fat infiltration in subjects with and without coronary artery disease. Frontiers in cardiovascular medicine. 2016;3:2. doi: 10.3389/fcvm.2016.00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Muiya N, Al-Najai M, Tahir AI, Elhawari S, Gueco D, Andres E, Mazhar N, Altassan N, Meyer BF, Alshahid M, Dzimiri N. The 3’-UTR of the adiponectin Q gene harbours susceptibility loci for atherosclerosis and its metabolic risk traits. BMC medical genetics. 2013;13:14–127. doi: 10.1186/1471-2350-14-127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Esteghamati A, Mansournia N, Nakhjavani M, Mansournia MA, Nikzamir A, Abbasi M. Association of +45(T/G) and +276(G/T) polymorphisms in the adiponectin gene with coronary artery disease in a population of Iranian patients with type 2 diabetes. Molecular biology reports. 2012;39(4):3791–3797. doi: 10.1007/s11033-011-1156-9. [DOI] [PubMed] [Google Scholar]
- 6.Wang Y, Liu RX, Liu H. Association of adiponectin gene polymorphisms with hypertensive disorder complicating pregnancy and disorders of lipid metabolism. Genetics and molecular research. 2015;14(4):15213–15223. doi: 10.4238/2015.November.25.9. [DOI] [PubMed] [Google Scholar]
- 7.Udomsinprasert W, Tencomnao T, Honsawek S, Anomasiri W, Vejchapipat P, Chongsrisawat V, Poovorawan Y. +276 G/T single nucleotide polymorphism of the adiponectin gene is associated with the susceptibility to biliary atresia. World journal of pediatrics. 2012 Nov;8(4):328–34. doi: 10.1007/s12519-012-0377-x. [DOI] [PubMed] [Google Scholar]
- 8.Rizza S, Clementi F, Porzio O, Cardellini M, Savo A, Serino M, Chiricolo G, Romeo F, Lauro R, Federici M. Adiponectin isoforms are not associated with the severity of coronary atherosclerosis but with undiagnosed diabetes in patients affected by stable CAD. Nutrition, metabolism and cardiovascular diseases. 2009;19(1):54–60. doi: 10.1016/j.numecd.2007.12.001. [DOI] [PubMed] [Google Scholar]
- 9.Bacci S, Menzaghi C, Ercolino T, Ma X, Rauseo A, Salvemini L, Vigna C, Fanelli R, Di Mario U, Doria A, Trischitta V. The +276 G/T single nucleotide polymorphism of the adiponectin gene is associated with coronary artery disease in type 2 diabetic patients. Diabetes care. 2004;7(8):2015–2020. doi: 10.2337/diacare.27.8.2015. [DOI] [PubMed] [Google Scholar]
- 10.Filippi E, Sentinelli F, Romeo S, Arca M, Berni A, Tiberti C, Verrienti A, Fanelli M, Fallarino M, Sorropago G, Baroni MG. 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 (age <or=50 years) Journal of molecular medicine. 2005;83(9):711–719. doi: 10.1007/s00109-005-0667-z. [DOI] [PubMed] [Google Scholar]
- 11.Tureck LV, Leite N, Souza RL, da Silva Timossi L, Osiecki AC, Osiecki R, Alle LF. ADIPOQ single nucleotide polymorphism:Association with adiponectin and lipoproteins levels restricted to men. Meta gene. 2015;5:98–104. doi: 10.1016/j.mgene.2015.06.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Arikoglu H, Ozdemir H, Kaya DE, Ipekci SH, Arslan A, Kayis SA, Gonen MS. The Adiponectin variants contribute to the genetic background of type 2 diabetes in Turkish population. Gene. 2014;534(1):10–16. [PubMed] [Google Scholar]