Micro R-410 Binding Site Single Nucleotide Polymorphism rs13702 in Lipoprotein Lipase Gene is Effective to Increase Susceptibility to Type 2 Diabetes in Iranian Population

Authors
Zahra Hatefi 1
Goljahan Soltani 1
Sharifeh Khosravi 1
Mohammad Kazemi 1
Ahmad Reza Salehi 1
Rasoul Salehi 2
1 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences; Gerfa Namayesh Azmayesh (GENAZMA) Science and Research Institute, Isfahan, Iran
Abstract
Background: The relationship between dyslipidemia and type 2 diabetes mellitus (T2DM) has been frequently reported. Lipoprotein lipase (LPL) is considered to be an effective gene in regulating lipid profile. MicroRNAs (miRNAs) are small noncoding RNAs involved in posttranscriptional regulation of gene expression. In the present study, we have evaluated rs13702 (C/T) polymorphism located in miRNA-410 binding site of LPL gene in subset of Iranian T2DM patients and their normal counterparts. Materials and Methods: In this case–control study, 102 T2DM patients and 98 healthy controls were worked out for rs13702 single nucleotide polymorphism genotypes. High resolution meting (HRM) analysis was used for genotyping. Results: C allele of rs13702 C/T polymorphism located in miRNA-410 binding site in LPL gene was detected to be significantly associated with T2DM (C allele; odds ratios (OR) = 1.729 (95% confidential intervals (CI) = 1.184–2.523); P = 0.005) also its CC genotype (OR = 3.28 (95% CI 8.68–1.24); P = 0.010) showed the same association. Conclusion: Correlation of rs13702 C allele with susceptibility to T2DM may be due to the higher level of LPL that leads to increased plasma fatty acids and its entry into peripheral tissues such as skeletal muscle, liver, and adipocytes causing development of insulin resistance and ultimately T2DM.

Keywords

1.
Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011;94:311-21.  Back to cited text no. 1
    
2.
Cai Y, Yu X, Hu S, Yu J. A brief review on the mechanisms of miRNA regulation. Genomics Proteomics Bioinformatics 2009;7:147-54.  Back to cited text no. 2
[PUBMED]    
3.
Kong L, Zhu J, Han W, Jiang X, Xu M, Zhao Y, et al. Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: A clinical study. Acta Diabetol 2011;48:61-9.  Back to cited text no. 3
[PUBMED]    
4.
Gong W, Xiao D, Ming G, Yin J, Zhou H, Liu Z, et al. Type 2 diabetes mellitus-related genetic polymorphisms in microRNAs and microRNA target sites. J Diabetes 2014;6:279-89.  Back to cited text no. 4
    
5.
Elek Z, Németh N, Nagy G, Németh H, Somogyi A, Hosszufalusi N, et al. Micro-RNA binding site polymorphisms in the WFS1 gene are risk factors of diabetes mellitus. PLoS One 2015;10:e0139519.  Back to cited text no. 5
    
6.
Zhao X, Ye Q, Xu K, Cheng J, Gao Y, Li Q, et al. Single-nucleotide polymorphisms inside microRNA target sites influence the susceptibility to type 2 diabetes. J Hum Genet 2013;58:135-41.  Back to cited text no. 6
[PUBMED]    
7.
Olivecrona G. Role of lipoprotein lipase in lipid metabolism. Curr Opin Lipidol 2016;27:233-41.  Back to cited text no. 7
[PUBMED]    
8.
Rodrigues R, Artieda M, Tejedor D, Martínez A, Konstantinova P, Petry H, et al. Pathogenic classification of LPL gene variants reported to be associated with LPL deficiency. J Clin Lipidol 2016;10:394-409.  Back to cited text no. 8
    
9.
Daoud MS, Ataya FS, Fouad D, Alhazzani A, Shehata AI, Al-Jafari AA, et al. Associations of three lipoprotein lipase gene polymorphisms, lipid profiles and coronary artery disease. Biomed Rep 2013;1:573-82.  Back to cited text no. 9
    
10.
Liu G, Xu JN, Liu D, Ding Q, Liu MN, Chen R, et al. Regulation of plasma lipid homeostasis by hepatic lipoprotein lipase in adult mice. J Lipid Res 2016;57:1155-61.  Back to cited text no. 10
[PUBMED]    
11.
Hassing HC, Surendran RP, Mooij HL, Stroes ES, Nieuwdorp M, Dallinga-Thie GM, et al. Pathophysiology of hypertriglyceridemia. Biochim Biophys Acta 2012;1821:826-32.  Back to cited text no. 11
    
12.
Richardson K, Nettleton JA, Rotllan N, Tanaka T, Smith CE, Lai CQ, et al. Gain-of-function lipoprotein lipase variant rs13702 modulates lipid traits through disruption of a microRNA-410 seed site. Am J Hum Genet 2013;92:5-14.  Back to cited text no. 12
[PUBMED]    
13.
Kim JK, Fillmore JJ, Chen Y, Yu C, Moore IK, Pypaert M, et al. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci U S A 2001;98:7522-7.  Back to cited text no. 13
[PUBMED]    
14.
Walton RG, Zhu B, Unal R, Spencer M, Sunkara M, Morris AJ, et al. Increasing adipocyte lipoprotein lipase improves glucose metabolism in high fat diet-induced obesity. J Biol Chem 2015;290:11547-56.  Back to cited text no. 14
[PUBMED]    
15.
Kalmár T, Seres I, Balogh Z, Káplár M, Winkler G, Paragh G, et al. Correlation between the activities of lipoprotein lipase and paraoxonase in type 2 diabetes mellitus. Diabetes Metab 2005;31:574-80.  Back to cited text no. 15
    
16.
Cho YS, Go MJ, Han HR, Cha SH, Kim HT, Min H, et al. Association of lipoprotein lipase (LPL) single nucleotide polymorphisms with type 2 diabetes mellitus. Exp Mol Med 2008;40:523-32.  Back to cited text no. 16
[PUBMED]    
17.
Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963;1:785-9.  Back to cited text no. 17
[PUBMED]    
18.
Boden G, Lebed B, Schatz M, Homko C, Lemieux S. Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects. Diabetes 2001;50:1612-7.  Back to cited text no. 18
[PUBMED]    
19.
Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004;114:1752-61.  Back to cited text no. 19
[PUBMED]    
20.
Guo W, Wong S, Xie W, Lei T, Luo Z. Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes. Am J Physiol Endocrinol Metab 2007;293:E576-86.  Back to cited text no. 20
[PUBMED]    
21.
Wei Y, Wang D, Topczewski F, Pagliassotti MJ. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells. Am J Physiol Endocrinol Metab 2006;291:E275-81.  Back to cited text no. 21
[PUBMED]    
22.
Karaskov E, Scott C, Zhang L, Teodoro T, Ravazzola M, Volchuk A, et al. Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress, which may contribute to INS-1 pancreatic beta-cell apoptosis. Endocrinology 2006;147:3398-407.  Back to cited text no. 22
    
23.
Kharroubi I, Ladrière L, Cardozo AK, Dogusan Z, Cnop M, Eizirik DL, et al. Free fatty acids and cytokines induce pancreatic beta-cell apoptosis by different mechanisms: Role of nuclear factor-kappaB and endoplasmic reticulum stress. Endocrinology 2004;145:5087-96.  Back to cited text no. 23
Advanced Biomedical Research
Volume 2018, May
May 2018
Pages 1-4