Identification of a New Single-nucleotide Polymorphism within the Apolipoprotein A5 Gene, Which is Associated with Metabolic Syndrome

Document Type : Original Article

Authors

1 Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran

2 Department of Genetics, Faculty of Basic Sciences, Shahrekord University; Research Institute of Biotechnology, Shahrekord University, Shahrekord, Iran

3 Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Paediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan, Iran

5 Department of Genetics and Molecular Biology, Faculty of Medicine; Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Metabolic syndrome (MetS) is a common disorder which is a constellation of clinical features including abdominal obesity, increased level of serum triglycerides (TGs) and decrease of serum high-density lipoprotein-cholesterol (HDL-C), elevated blood pressure, and glucose intolerance. The apolipoprotein A5 (APOA5) is involved in lipid metabolism, influencing the level of plasma TG and HDL-C. In the present study, we aimed to investigate the associations between four INDEL variants of APOA5 gene and the MetS risk. Materials and Methods: In this case–control study, we genotyped 116 Iranian children and adolescents with/without MetS by using Sanger sequencing method for these INDELs. Then, we explored the association of INDELs with MetS risk and their clinical components by logistic regression and one-way analysis of variance analyses. Results: We identified a novel insertion polymorphism, c. *282–283 insAG/c. *282–283 insG variant, which appears among case and control groups. rs72525532 showed a significant difference for TG levels between various genotype groups. In addition, there were significant associations between newly identified single-nucleotide polymorphism (SNP) and rs72525532 with MetS risk. Conclusions: These results show that rs72525532 and the newly identified SNP may influence the susceptibility of the individuals to MetS.

Keywords

1.
Isomaa B, Almgren P, Tuomi T, Forsén B, Lahti K, Nissén M, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683-9.  Back to cited text no. 1
    
2.
Alberti KG, Zimmet P, Shaw J. The metabolic syndrome – A new worldwide definition. A consensus statement from the International Diabetes Federation. Lancet 2005;366:1059-62.  Back to cited text no. 2
    
3.
Roche HM, Phillips C, Gibney MJ. The metabolic syndrome: The crossroads of diet and genetics. Proc Nutr Soc 2005;64:371-7.  Back to cited text no. 3
    
4.
Kelishadi R, Ardalan G, Gheiratmand R, Adeli K, Delavari A, Majdzadeh R. Caspian Study Group. Paediatric metabolic syndrome and associated anthropometric indices: The CASPIAN study. Acta Paediatr 2006;95:1625-34.  Back to cited text no. 4
    
5.
Pennacchio LA, Olivier M, Hubacek JA, Cohen JC, Cox DR, Fruchart JC, et al. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 2001;294:169-73.  Back to cited text no. 5
    
6.
Hodoglugil U, Tanyolaç S, Williamson DW, Huang Y, Mahley RW. Apolipoprotein A-V: A potential modulator of plasma triglyceride levels in Turks. J Lipid Res 2006;47:144-53.  Back to cited text no. 6
    
7.
Hubacek JA. Apolipoprotein A5 and triglyceridemia. Focus on the effects of the common variants. Clin Chem Lab Med 2005;43:897-902.  Back to cited text no. 7
    
8.
Nilsson SK, Heeren J, Olivecrona G, Merkel M. Apolipoprotein A-V; a potent triglyceride reducer. Atherosclerosis 2011;219:15-21.  Back to cited text no. 8
    
9.
Halalkhor S, Jalali F, Tilaki KH, Shojaei S. Association of two common polymorphisms of apolipoprotein A5 gene with metabolic syndrome indicators in a North Iranian population, a cross-sectional study. J Diabetes Metab Disord 2014;13:48.  Back to cited text no. 9
    
10.
Fallah MS, Sedaghatikhayat B, Guity K, Akbari F, Azizi F, Daneshpour M. The relation between metabolic syndrome risk factors and genetic variations of apolipoprotein V in relation with serum triglyceride and HDL-C Level. Arch Iran Med 2016;19:46-50.  Back to cited text no. 10
    
11.
Rottiers V, Näär AM. MicroRNAs in metabolism and metabolic disorders. Mol Cell Biol 2012;13:239-51.  Back to cited text no. 11
    
12.
Gong J, Tong Y, Zhang HM, Wang K, Hu T, Shan G, et al. Genome-wide identification of SNPs in microRNA genes and the SNP effects on microRNA target binding and biogenesis. Hum Mutat 2012;33:254-63.  Back to cited text no. 12
    
13.
Heneghan HM, Miller N, Kerin MJ. Role of microRNAs in obesity and the metabolic syndrome. Obes Rev 2010;11:354-61.  Back to cited text no. 13
    
14.
Hu Z, Bruno AE. The influence of 3'UTRs on MicroRNA function inferred from human SNP data. Comp Funct Genomics 2011;2011:910769.  Back to cited text no. 14
    
15.
Lin PC, Liu TC, Chang CC, Chen YH, Chang JG. High-resolution melting (HRM) analysis for the detection of single nucleotide polymorphisms in microRNA target sites. Clin Chim Acta 2012;413:1092-7.  Back to cited text no. 15
    
16.
Ziebarth JD, Bhattacharya A, Chen A, Cui Y. PolymiRTS database 2.0: Linking polymorphisms in microRNA target sites with human diseases and complex traits. Nucleic Acids Res 2012;40:D216-21.  Back to cited text no. 16
    
17.
Sethupathy P, Collins FS. MicroRNA target site polymorphisms and human disease. Trends Genet 2008;24:489-97.  Back to cited text no. 17
    
18.
Bandiera S, Hatem E, Lyonnet S, Henrion-Caude A. MicroRNAs in diseases: From candidate to modifier genes. Clin Genet 2010;77:306-13.  Back to cited text no. 18
    
19.
Bao BY, Pao JB, Huang CN, Pu YS, Chang TY, Lan YH, et al. Polymorphisms inside microRNAs and microRNA target sites predict clinical outcomes in prostate cancer patients receiving androgen-deprivation therapy. Clin Cancer Res 2011;17:928-36.  Back to cited text no. 19
    
20.
Chen K, Song F, Calin GA, Wei Q, Hao X, Zhang W. Polymorphisms in microRNA targets: A gold mine for molecular epidemiology. Carcinogenesis 2008;29:1306-11.  Back to cited text no. 20
    
21.
Ryan BM, Robles AI, Harris CC. Genetic variation in microRNA networks: The implications for cancer research. Nat Rev Cancer 2010;10:389-402.  Back to cited text no. 21
    
22.
Wang G, van der Walt JM, Mayhew G, Li YJ, Züchner S, Scott WK, et al. Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein. Am J Hum Genet 2008;82:283-9.  Back to cited text no. 22
    
23.
Lei SF, Papasian CJ, Deng HW. Polymorphisms in predicted miRNA binding sites and osteoporosis. J Bone Miner Res 2011;26:72-8.  Back to cited text no. 23
    
24.
Lv K, Guo Y, Zhang Y, Wang K, Jia Y, Sun S. Allele-specific targeting of hsa-miR-657 to human IGF2R creates a potential mechanism underlying the association of ACAA-insertion/deletion polymorphism with type 2 diabetes. Biochem Biophys Res Commun 2008;374:101-5.  Back to cited text no. 24
    
25.
Martin MM, Buckenberger JA, Jiang J, Malana GE, Nuovo GJ, Chotani M, et al. The human angiotensin II type 1 receptor + 1166 A/C polymorphism attenuates microRNA-155 binding. J Biol Chem 2007;282:24262-9.  Back to cited text no. 25
    
26.
Update on the task force report on high blood pressure in children and adolescents: A working group report from the National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. Pediatrics 1996;98(4 Pt 1):649-58.  Back to cited text no. 26
    
27.
Bao L, Zhou M, Wu L, Lu L, Goldowitz D, Williams RW, et al. PolymiRTS database: Linking polymorphisms in microRNA target sites with complex traits. Nucleic Acids Res 2007;35:D51-4.  Back to cited text no. 27
    
28.
Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005;120:15-20.  Back to cited text no. 28
    
29.
Betel D, Wilson M, Gabow A, Marks DS, Sander C. The microRNA.org resource: Targets and expression. Nucleic Acids Res 2008;36:D149-53.  Back to cited text no. 29
    
30.
Kraja AT, Vaidya D, Pankow JS, Goodarzi MO, Assimes TL, Kullo IJ, et al. A bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium. Diabetes 2011;60:1329-39.  Back to cited text no. 30
    
31.
Ye Q, Zhao X, Xu K, Li Q, Cheng J, Gao Y, et al. Polymorphisms in lipid metabolism related miRNA binding sites and risk of metabolic syndrome. Gene 2013;528:132-8.  Back to cited text no. 31