Association of rs780094 and rs1260326 glucokinase regulatory protein gene polymorphisms with dyslipidemia in a group of Serbian acute ischemic stroke patients

Authors

DOI:

https://doi.org/10.2298/ABS211126002B

Keywords:

Acute ischemic stroke, glucokinase regulatory protein, rs780094, rs1260326, lipid profile

Abstract

Paper description:

  • Single nucleotide polymorphisms (SNPs) rs780094 and rs1260326 of the glucokinase regulatory protein gene (GCKR) could be associated with dyslipidemia, a leading risk factor for acute ischemic stroke (AIS) development.
  • The influence of GCKR rs780094 and rs1260326 SNPs on the lipid profile and the association of these SNPs with the risk of AIS were assessed.
  • The rs780094TT genotype and the rs1260326TT genotype were associated with decreased risk for AIS.
  • This study provides a foundation for a better understanding of the biological basis of the influence of GCKR rs780094 and rs1260326 SNPs on AIS development.

Abstract: Although genetic variations rs780094 and rs1260326 of the glucokinase regulatory protein gene (GCKR) could be associated with lipid profile imbalance, their influence on acute ischemic stroke (AIS) risk has not yet been established. The aim of this study was to investigate the influence of GCKR single nucleotide polymorphisms (SNPs) rs780094 and rs1260326 on lipid profile parameters in patients with AIS, and to evaluate the association of these SNPs with the risk of AIS. In a case-control study, a total of 148 subjects were screened for GCKR rs780094 and rs1260326 SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The lipid profile was determined based on serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triacylglycerol (TG) concentrations. The frequencies of the minor rs780094T allele and the minor rs1260326T allele were significantly lower in AIS patients compared to controls. The rs780094TT genotype and the rs1260326TT genotype were associated with decreased risk of AIS compared to wildtype carriers. In conclusion, this is the first study implying that decreased risk of AIS in rs780094 and rs1260326 homozygous minor allele carriers is not caused by dyslipidemia, but possibly by the lack of coagulation factor glycosylation.

Downloads

Download data is not yet available.

References

AHA/ASA Expert Consensus Document: An updated definition of stroke for the 21st century a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44:2064-89.

Sommer CJ. Ischemic stroke: experimental models and reality. Acta Neuropathol. 2017;133(2):245-61. https://doi.org/10.1007/s00401-017-1667-0

Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, Chaturvedi S, Creager MA, Eckel RH, Elkind MSV, Fornage M, Goldstein LB, Greenberg SM, Horvath SE, Iadecola C, Jauch EC, Moore WS, Wilson JA. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(12):3754-832. https://doi.org/10.1161/STR.0000000000000046

Shahar E, Chambless LE, Rosamond WD, Boland LL, Ballantyne CM, McGovern PG, Sharrett AR. Plasma lipid profile and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2003;34(3):623-31. https://doi.org/10.1161/01.STR.0000057812.51734.FF

Zhou YJ, Hong SC, Yin RX, Yang Q, Cao XL, Chen WX. Polymorphisms in the GCKR are associated with serum lipid traits, the risk of coronary artery disease and ischemic stroke. Int J Clin Exp Med. 2015;8(7):10678-86.

Perez-Martinez P, Corella D, Shen J Arnett DK, Yiannakouris N, Tai ES, Orho-Melander M, Tucker KL, Tsai M, Straka RJ, Province M, Kai CS, Perez-Jimenez F, Lai CQ, Lopez-Miranda J, Guillen M, Parnell LD, Borecki I, Kathiresan S, Ordovas JM. Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states. Am J Clin Nutr. 2008;89(1):391-9. https://doi.org/10.3945/ajcn.2008.26363

Pollin TI, Jablonski KA, McAteer JB Saxena R, Kathiresan S, Kahn SE, Goldberg RB, Altshuler D, Florez JC. Triglyceride response to an intensive lifestyle intervention is enhanced in carriers of the GCKR Pro446Leu polymorphism. J Clin Endocrinol Metab. 2011;96(7):E1142-7. https://doi.org/10.1210/jc.2010-2324

Mohás M, Kisfali P, Járomi L, Maász A, Fehér E, Csöngei V, Polgár N, Sáfrány E, Cseh J, Sümegi K, Hetyésy K, Wittmann I, Melegh B. GCKR gene functional variants in type 2 diabetes and metabolic syndrome: do the rare variants associate with increased carotid intima-media thickness? Cardiovasc Diabetol. 2010;9:79. https://doi.org/10.1186/1475-2840-9-79

Transcript: GCKR-201. Ensembl genome browser 104 for Human GCKR gene [Internet]. EMBL-EBI. Ensembl release 104 - November 2021 [Cited 2021 Nov 18]. Available from: http://www.ensembl.org/Homo_sapiens/Transcript/Summary?db=core;g=ENSG00000084734;r=2:27496839-27523684;t=ENST00000264717

Shen H, Pollin TI, Damcott CM, McLenithan JC, Mitchell BD, Shuldiner AR. Glucokinase regulatory protein gene polymorphism affects postprandial lipemic response in a dietary intervention study. Hum Genet. 2009;126(4):567-74. https://doi.org/10.1007/s00439-009-0700-3

Bi M, Kao WH, Boerwinkle E, Hoogeveen RC, Rasmussen-Torvik LJ, Astor BC, North KE, Coresh J, Kottgen A. Association of rs780094 in GCKR with Metabolic Traits and Incident Diabetes and Cardiovascular Disease: The ARIC Study. PLoS One. 2010;5(7):e11690. https://doi.org/10.1371/journal.pone.0011690

Járomi L, Csöngei V, Polgár N, Szolnoki Z, Maász A, Horvatovich K, Faragó B, Sipeky C, Sáfrány E, Magyari L, Kisfali P, Mohás M, Janicsek I, Lakner L, Melegh B. Functional variants of glucokinase regulatory protein and apolipoprotein A5 genes in ischemic stroke. J Mol Neurosci. 2010;41:121-8. https://doi.org/10.1007/s12031-009-9301-9

Beer NL, Tribble ND, McCulloch LJ Roos C, Johnson PRV, Orho-Melander M, Gloyn AL. The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver. Hum Mol Genet. 2009;18(21):4081-8. https://doi.org/10.1093/hmg/ddp357

Rees MG, Wincovitch S, Schultz J, Waterstradt R, Beer NL, Baltrusch S, Collins FS, Gloyn AL. Cellular characterisation of the GCKR P446L variant associated with type 2 diabetes risk. Diabetologia. 2012; 55(1): 114-22. https://doi.org/10.1007/s00125-011-2348-5

Raimondo A, Rees MG, Gloyn AL. Glucokinase regulatory protein: complexity at the crossroads of triglyceride and glucose metabolism. Curr Opin Lipidol. 2015;26(2):88-95. https://doi.org/10.1097/MOL.0000000000000155

López Rodríguez M, Kaminska D, Lappalainen K, Pihlajamäki J, Kaikkonen MU, Laakso M. Identification and characterization of a FOXA2-regulated transcriptional enhancer at a type 2 diabetes intronic locus that controls GCKR expression in liver cells. Genome Med. 2017;9(1):63. https://doi.org/10.1186/s13073-017-0453-x

Onuma H, Tabara Y, Kawamoto R Shimizu I, Kawamura R, Takata Y, Nishida W, Ohashi J, Miki T, Kohara K, Makino H, Osawa H. The GCKR rs780094 polymorphism is associated with susceptibility of type 2 diabetes, reduced fasting plasma glucose levels, increased triglycerides levels and lower HOMA-IR in Japanese population. J Hum Genet. 2010;55(9):600-4. https://doi.org/10.1038/jhg.2010.75

Vaxillaire M, Cavalcanti-Proença C, Dechaume A, Tichet J, Marre M, Balkau B, Froguel P. The common P446L polymorphism in GCKR inversely modulates fasting glucose and triglyceride levels and reduces type 2 diabetes risk in the DESIR prospective general French population. Diabetes. 2008;57(8):2253-7. https://doi.org/10.2337/db07-1807

Sennblad B, Basu S, Mazur J, Suchon P, Martinez-Perez A, van Hylckama Vlieg A, Truong V, Li Y, Gådin JR, Tang W, Grossman V, de Haan HG, Handin N, Silveira A, Souto JC, Franco-Cereceda A, Morange PE, Gagnon F, Soria JM, Eriksson P, Hamsten A, Maegdefessel L, Rosendaal FR, Wild P, Folsom AR, Trégouët DA, Sabater-Lleal M. Genome-wide association study with additional genetic and post-transcriptional analyses reveals novel regulators of plasma factor XI levels. Hum Mol Genet. 2017;26(3):637-49. https://doi.org/10.1093/hmg/ddw401

Jevtovic Stoimenov T, Despotovic M, Stojanovic S, Basic J, Pavlovic D. Polymorphic variants of antioxidative defense enzymes and their gene-gene epistatic interactions in systemic lupus erythematodes patients. Clin Rheumatol. 2017;36(9):2019-26. https://doi.org/10.1007/s10067-017-3755-x

Despotovic M, Jevtovic Stoimenov T, Stankovic I, Basic J, Pavlovic D. Vitamin D Receptor Gene Polymorphisms in Serbian Patients with Bronchial Asthma: A Case-ControlStudy. J Cell Biochem. 2017;118(11):3986-92. https://doi.org/10.1002/jcb.26054

Despotović M, Jevtović Stoimenov T, Stojanović S, Bašić J, Kundalić J, Đorđević B, Ranđelović M., Pavlović D. Association of vitamin D receptor genetic variants with bone mineral density and inflammatory markers in rheumatoid arthritis. Clin Biochem. 2021;87:26-31. https://doi.org/10.1016/j.clinbiochem.2020.10.006

Despotović M, Jevtović Stoimenov T, Stanković I, Bašić J, Đorđević B. Genetic variants of vitamin D receptor and antioxidant enzyme genes in bronchial asthma: Epistatic interactions. Ann Allergy Asthma Immunol. 2020;125(6):701-3. https://doi.org/10.1016/j.anai.2020.07.020

Bašić J, Milošević V, Stanković M, Jevtović-Stoimenov T, Cvetković T, Despotović M, Pavlović D. The influence of rs53576 and rs2254298 oxytocin receptor gene polymorphisms on plasma oxytocin levels and measures of empathy. Arch Biol Sci. 2019;71(1):159-65. https://doi.org/10.2298/ABS181206057B

Man AWC, Li H, Xia N. Impact of Lifestyles (Diet and Exercise) on Vascular Health: Oxidative Stress and Endothelial Function. Oxid Med Cell Longev. 2020;2020:1496462. https://doi.org/10.1155/2020/1496462

Ljubisavljevic S, Stojanovic I, Pavlovic R, Pavlovic D. The importance of nitric oxide and arginase in the pathogenesis of acute neuroinflammation: are those contra players with the same direction? Neurotox Res. 2014;26(4):392-9. https://doi.org/10.1007/s12640-014-9470-3

Ljubisavljevic S, Stojanovic I, Pavlovic R, Sokolovic D, Pavlovic D, Cvetkovic T, Stevanovic I. Modulation of nitric oxide synthase by arginase and methylated arginines during the acute phase of experimental multiple sclerosis. J Neurol Sci. 2012;318(1-2):106-11. https://doi.org/10.1016/j.jns.2012.03.015

Downloads

Published

2022-04-01

How to Cite

1.
Bašić J, Milošević V, Živanović M, Kundalić J, Despotović M, Jevtović-Stoimenov T, Stojanović I. Association of rs780094 and rs1260326 glucokinase regulatory protein gene polymorphisms with dyslipidemia in a group of Serbian acute ischemic stroke patients. Arch Biol Sci [Internet]. 2022Apr.1 [cited 2022Jul.6];74(1):41-7. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/7269

Issue

Section

Articles

Most read articles by the same author(s)