Lipoprotein lipase gene polymorphisms as risk factors for stroke: a computational and meta-analysis

Document Type : Original Article

Authors

Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran

Abstract

Objective(s): Stroke is the most common neurological disorder and genetic susceptibility has an important role in its etiology. Polymorphism in several genes such as lipoprotein lipase (LPL) is propounded as a risk for stroke. This meta-analysis investigated the association of rs285 and rs320 LPL polymorphism with stroke risk.
Materials and Methods: We searched PubMed, Clarivate Analytics Web of Science, Google Scholar, and Science Direct databases for appropriate studies. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of this association. Also, the effects of four common polymorphisms (rs268, rs285, rs320, and rs328) on the molecular aspects of LPL were evaluated by in silico tools. Five studies were included in meta-analysis after screening.
Results: Our data indicated that rs320 significantly decreased the risk of stroke (G vs. T: OR= 0.64, 95%CI=0.54-0.76; GG vs. TT: OR=0.47, 95%CI=0.29-0.75; TG vs. TT: OR=0.65, 95%CI=0.53-0.80; TG+GG vs. TT: OR=0.62, 95%CI=0.51-0.75; GG vs. TT+TG: OR=0.51, 95%CI=0.32-0.82). Moreover, a significant association between rs285 and diminution of stroke risk was seen (P- vs. P+: OR=0.72, 95%CI=0.58-0.91; P-P- vs. P+P+: OR=0.50, 95%CI=0.31-0.82; P+P-+P-P- vs. P+P+: OR=0.72, 95%CI=0.53-0.96; P-P- vs. P+P++P+P-: OR=0.581, 95%CI=0.369-0.916). Also, the same results were observed after stratifying, without any publication bias (PEgger>0.05). Furthermore, computational analysis revealed that rs268 and rs328 may affect the protein structure (prediction: non-neutral; score=19; expected accuracy=59%) while rs320 could affect the RNA structure (distance=0.2264, P-value=0.0534; PConclusion: This meta-analysis indicated that risk of stroke was decreased in rs320 and rs285 polymorphisms in the LPL gene.

Keywords

Main Subjects

References

1. Frizzell JP. Acute stroke: pathophysiology, diagnosis, and treatment. AACN Clin Issues 2005;16:421-440.
2. Poorthuis MH, Algra AM, Algra A, Kappelle LJ, Klijn CJ. Female-and Male-Specific Risk Factors for Stroke: A Systematic Review and Meta-analysis. JAMA Neurol. 2017;74:75-81.
3. Raffeld MR, Debette S, Woo D. International Stroke Genetics Consortium Update. Stroke 2016;47:1144-1145.
4. Park J-H, Kwon H-M, Ovbiagele B. New Pooled Cohort Risk equations: Application to a recent stroke patient population. Journal of the neurological sciences. 2015;348(1):160-165.
5. Chauhan G, Debette S. Genetic Risk Factors for Ischemic and Hemorrhagic Stroke. J Neurol Sci 2015;348:160-165.
6. Zhu Z, Yan J, Geng C, Wang D, Li C, Feng S, et al. A polymorphism Within the 3′ UTR of NLRP3 is associated with susceptibility for ischemic stroke in chinese population. Cell Mol Neurobiol 2016;36:981-988.
7. Yang J, Wu B, Lin S, Zhou J, Li Y, Dong W, et al. Genetic variations of MMP9 gene and intracerebral hemorrhage susceptibility: A case–control study in Chinese Han population. J Neurol Sci 2014;341:55-57.
8. Cao L, Zhang Z, Cai B, Bai W, Zhang Y, Sun W, et al. Association of heme oxygenase-1 gene rs2071746 polymorphism with vascular outcomes in patients with atherosclerotic stroke. J Neurol Sci 2014;344:154-157.
9. Sun H, Wu H, Zhang J, Wang J, Lu Y, Ding H, et al. A tagging SNP in ALOX5AP and risk of stroke: a haplotype-based analysis among eastern Chinese Han population. Mol Biol Rep 2011;38:4731-4738.
10. Xing H-X, Guo S-X, Zhang Y, Zhang X-Y. Relationship between lipoprotein lipase gene polymorphism and hemorrhagic stroke in a Chinese population. Int J Clin Exp Med 2015;8:13592-13597.
11. Wang C, Sun T, Li H, Bai J, Li Y. Lipoprotein lipase Ser447Ter polymorphism associated with the risk of ischemic stroke: a meta-analysis. Thromb Res 2011;128:107-112.
12. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-560.
13. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies. J Natl Cancer Inst 1959;22:719-748.
14. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-188.
15. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088-101.
16. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-634.
17. Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Bio 1982;157:105-132.
18. Bhaskaran R, Ponnuswamy P. Positional flexibilities of amino acid residues in globular proteins. Int J Pept Protein Res 1988;32:241-155.
19. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods 2010;7:248-249.
20. Bromberg Y, Rost B. SNAP: predict effect of non-synonymous polymorphisms on function. Nucleic Acids Res 2007;35:3823-3835.
21. Hebsgaard SM, Korning PG, Tolstrup N, Engelbrecht J, Rouzé P, Brunak S. Splice site prediction in Arabidopsis thaliana pre-mRNA by combining local and global sequence information. Nucleic Acids Res 1996;24:3439-3452.
22. Sabarinathan R, Tafer H, Seemann SE, Hofacker IL, Stadler PF, Gorodkin J. The RNAsnp web server: predicting SNP effects on local RNA secondary structure. Nucleic Acids Res 2013;41:W475-W479.
23. Gu B, Zhao Y-C, Yang Z-W, Li H-T, Yu F-P. HindIII polymorphism in the lipoprotein lipase gene and hypertensive intracerebral hemorrhage in the Chinese Han population. J Stroke Cerebrovasc Dis 2014;23:1275-1281.
24. Zhang W-S, Zhang W-H, Liu Q-J. Lipoprotein lipase gene Hind III polymorphism was associated with hemorrhagic stroke. Int J Clin Exp Med 2015;8:9575-9579.
25. Xu E, Li W, Zhan L, Guan G, Wang X, Chen S, et al. Polymorphisms of the lipoprotein lipase gene are associated with atherosclerotic cerebral infarction in the Chinese. Neuroscience 2008;155:403-408.
26. Shimo-Nakanishi Y, Urabe T, Hattori N, Watanabe Y, Nagao T, Yokochi M, et al. Polymorphism of the lipoprotein lipase gene and risk of atherothrombotic cerebral infarction in the Japanese. Stroke 2001;32:1481-1486.
27. Knapp L, Gellért L, Kocsis K, Kis Z, Farkas T, Vécsei L, et al. Neuroprotective effect of oxaloacetate in a focal brain ischemic model in the rat. Cell Mol Neurobiol 2015;35:17-22.
28. Rubattu S, Stanzione R, Gigante B, Volpe M. Role of genetic factors in the etiopathogenesis of cerebrovascular accidents: from an animal model to the human disease. Cell Mol Neurobiol 2004;24:581-588.
29. Johnston SC, Rothwell PM, Nguyen-Huynh MN, Giles MF, Elkins JS, Bernstein AL, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet 2007;369:283-292.
30. Titov B, Matveeva N, Martynov MY, Favorova O. Ischemic stroke as a complex polygenic disease. Mol Biol 2015;49:195-216.
31. Munshi A, Babu MS, Kaul S, Rajeshwar K, Balakrishna N, Jyothy A. Association of LPL gene variant and LDL, HDL, VLDL cholesterol and triglyceride levels with ischemic stroke and its subtypes. J Neurol Sci 2012;318:51-54.
32. Goldberg IJ. Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. J Lipid Res 1996;37:693-707.
33. Pingitore P, Lepore SM, Pirazzi C, Mancina RM, Motta BM, Valenti L, et al. Identification and characterization of two novel mutations in the LPL gene causing type I hyperlipoproteinemia. J Clin Lipidol 2016; 10:816-823.
34. Nikzad H, Karimian M, Sareban K, Khoshsokhan M, Colagar AH. MTHFR-Ala222Val and male infertility: a study in Iranian men, an updated meta-analysis and an in silico-analysis. Reprod Biomed Online 2015;31:668-680.
35. Ebrahimi A, Hosseinzadeh Colagar A, Karimian M. Association of Human Methionine Synthase-A2756G Transition With Prostate Cancer: A Case-Control Study and in Silico Analysis. Acta Med Iran 2017;55:297-303.
36. Jamali S, Karimian M, Nikzad H, Aftabi Y. The c.− 190 C> A transversion in promoter region of protamine1 gene as a genetic risk factor for idiopathic oligozoospermia. Mol Biol Rep 2016;43:795-802.
37. Raygan F, Karimian M, Rezaeian A, Bahmani B, Behjati M. Angiotensinogen-M235T as a risk factor for myocardial infarction in Asian populations: a genetic association study and a bioinformatics approach. Croat Med J 2016;57:351-162.
38. Mazaheri M, Karimian M, Behjati M, Raygan F, Hosseinzadeh Colagar A. Association analysis of rs1049255 and rs4673 transitions in p22phox gene with coronary artery disease: A case-control study and a computational analysis. Ir J Med Sci 2017;186:921-928.
39. Karimian M, Hosseinzadeh Colagar. Methionine synthase A2756G transition might be a risk factor for male infertility: Evidences from seven case-control studies. Mol Cell Endocrinol 2016;425:1-10.
40. Karimian M, Hosseinzadeh Colagar A. Human MTHFR-G1793A transition may be a protective mutation against male infertility: a genetic association study and in silico analysis. Hum Fertil 2018;21:128-136.
Iranian Journal of Basic Medical Sciences
Volume 21, Issue 7
July 2018
Pages 701-708

Files

Share

How to cite

Statistics