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Association of the GCKR rs780094 polymorphism with metabolic traits including carotid intima-media thickness in Japanese community-dwelling men, but not in women

  • Fumi Murata-Mori , Naomi Hayashida , Takao Ando , Toshiyuki Ikeoka , Mio Nakazato , Harutaka Sekita , Norio Abiru , Hironori Yamasaki , Takahiro Maeda , Atsushi Kawakami and Noboru Takamura EMAIL logo
Published/Copyright: August 29, 2013

Abstract

Background: The glucokinase regulator gene (GCKR) rs780094 has been shown to be strongly associated with some metabolic traits and atherosclerotic parameters, while the association between GCKR rs780094 and carotid intima-media thickness (CIMT) has not been fully investigated in the general population. The associations between the GCKR rs780094 genotype and metabolic traits including CIMT were examined in a Japanese community-dwelling population.

Methods: A total of 2491 Japanese adults (907 men and 1584 women) who participated in a medical screening program for the general population from 29 to 94 years of age during 2008 to 2010 were enrolled. GCKR rs780094 was genotyped by the TaqMan polymerase chain reaction method, and associations with metabolic markers including CIMT were evaluated.

Results: GCKR rs780094 AA genotype was significantly associated with higher TG (p<0.001 vs. GG), lower HDL-C (p=0.021 vs. GG), and lower HbA1c(p=0.023 vs. GG). The AA genotype showed significantly thinner CIMT (p=0.001 vs. GX). These associations were seen only in men.

Conclusions: GCKR rs780094 was associated with TG, HDL-C, and HbA1c levels, as well as with CIMT in Japanese community-dwelling men, but not women.


Corresponding author: Noboru Takamura, MD, PhD, Professor and Chairman, Department of Global Health, Medicine and Welfare, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan, Phone: +81 95 8197170, Fax: +81 95 8197172, E-mail:

This study was supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (No. 21590699).

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

References

1. Van Schaftingen E, Detheux M, Veiga da Cunha M. Short-term control of glucokinase activity: role of a regulatory protein. FASEB J 1994;8:414–9.10.1096/fasebj.8.6.8168691Search in Google Scholar PubMed

2. Massa ML, Gagliardino JJ, Francini F. Liver glucokinase: an overview on the regulatory mechanisms of its activity. IUBMB Life 2011;63:1–6.10.1002/iub.411Search in Google Scholar PubMed

3. Iynedjian PB. Molecular physiology of mammalian glucokinase. Cell Mol Life Sci 2009;66:27–42.10.1007/s00018-008-8322-9Search in Google Scholar PubMed PubMed Central

4. Sparsø T, Andersen G, Nielsen T, Burgdorf KS, Gjesing AP, Nielsen AL, et al. The GCKR rs780094 polymorphism is associated with elevated fasting serum triacylglycerol, reduced fasting and OGTT-related insulinaemia, and reduced risk of type 2 diabetes. Diabetologia 2008;51:70–5.10.1007/s00125-007-0865-zSearch in Google Scholar PubMed

5. de la Iglesia N, Mukhtar M, Seoane J, Guinovart JJ, Agius L. The role of the regulatory protein of glucokinase in the glucose sensory mechanism of the hepatocyte. J Biol Chem 2000;275:10597–603.10.1074/jbc.275.14.10597Search in Google Scholar PubMed

6. Chu CA, Fujimoto Y, Igawa K, Grimsby J, Grippo JF, Magnuson MA, et al. Rapid translocation of hepatic glucokinase in response to intraduodenal glucose infusion and changes in plasma glucose and insulin in conscious rats. Am J Physiol Gastrointest Liver Physiol 2004;286:G627–34.10.1152/ajpgi.00218.2003Search in Google Scholar PubMed

7. Vaxillaire M, Cavalcanti-Proença C, Dechaume A, Tichet J, Marre M, Balkau B, et al. 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; 57:2253–7.10.2337/db07-1807Search in Google Scholar PubMed PubMed Central

8. Ridker PM, Pare G, Parker A, Zee RY, Danik JS, Buring JE, et al. Loci related to metabolic-syndrome pathways including LEPR, HNF1A, IL6R and GCKR associate with plasma C-reactive protein: the Women’s Genome Health Study. Am J Hum Genet 2008;82:1185–92.10.1016/j.ajhg.2008.03.015Search in Google Scholar PubMed PubMed Central

9. Speliotes EK, Yerges-Armstrong LM, Wu J, Hernaez R, Kim LJ, Palmer CD, et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet 2011;7:e1001324.Search in Google Scholar

10. Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 2010;42:105–16.10.1038/ng.520Search in Google Scholar PubMed PubMed Central

11. Qi Q, Wu Y, Li H, Loos RJ, Hu FB, Sun L, et al. Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population. Diabetologia 2009;52:834–43.10.1007/s00125-009-1290-2Search in Google Scholar PubMed

12. Bi M, Kao WH, Boerwinkle E, Hoogeveen RC, Rasmussen-Torvik LJ, Astor BC, et al. Association of rs780094 in GCKR with metabolic traits and incident diabetes and cardiovascular disease: the ARIC Study. PLoS One 2010;5:e11690.10.1371/journal.pone.0011690Search in Google Scholar PubMed PubMed Central

13. Onuma H, Tabara Y, Kawamoto R, Shimizu I, Kawamura R, Takata Y, et al. 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;55:600–4.10.1038/jhg.2010.75Search in Google Scholar PubMed

14. Yang Z, Wen J, Tao X, Lu B, Du Y, Wang M, et al. Genetic variation in the GCKR gene is associated with non-alcoholic fatty liver disease in Chinese people. Mol Biol Rep 2011;38:1145–50.10.1007/s11033-010-0212-1Search in Google Scholar PubMed

15. Johansen CT, Hegele RA. Genetic bases of hypertriglyceridemic phenotypes. Curr Opin Lipidol 2011;22:247–53.10.1097/MOL.0b013e3283471972Search in Google Scholar PubMed

16. Mohás M, Kisfali P, Járomi L, Maász A, Fehér E, Csöngei V, et al. 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;9:79.10.1186/1475-2840-9-79Search in Google Scholar PubMed PubMed Central

17. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 1999;340:14–22.10.1056/NEJM199901073400103Search in Google Scholar PubMed

18. Vigili de Kreutzenberg S, Tiengo A, Avogaro A. Cerebrovascular disease in diabetes mellitus: the role of carotid intima-media thickness. Nutr Metab Cardiovasc Dis 2009;19:667–73.10.1016/j.numecd.2009.03.014Search in Google Scholar PubMed

19. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 2007;115:459–67.10.1161/CIRCULATIONAHA.106.628875Search in Google Scholar PubMed

20. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499–502.10.1093/clinchem/18.6.499Search in Google Scholar

21. Kashiwagi A, Kasuga M, Araki E, Oka Y, Hanafusa T, Ito H, et al. International clinical harmonization of glycated hemoglobin in Japan: from Japan Diabetes Society to National Glycohemoglobin Standardization Program values. J Diabetes Invest 2012;3:39–40.10.1111/j.2040-1124.2012.00207.xSearch in Google Scholar PubMed PubMed Central

22. Stančáková A, Paananen J, Soininen P, Kangas AJ, Bonnycastle LL, Morken MA, et al. Effects of 34 risk loci for type 2 diabetes or hyperglycemia on lipoprotein subclasses and their composition in 6,580 nondiabetic Finnish men. Diabetes 2011;60:1608–16.10.2337/db10-1655Search in Google Scholar

23. Ordovas JM. Gender, a significant factor in the cross talk between genes, environment, and health. Gend Med 2007;4(Suppl B):S111–22.10.1016/S1550-8579(07)80052-0Search in Google Scholar

24. Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. New Engl J Med 1999;340:1801–11.10.1056/NEJM199906103402306Search in Google Scholar PubMed

25. Kozàkovà M, Palombo C, Morizzo C, Nolan JJ, Konrad T, Dekker JM, et al. Gender-specific differences in carotid intima-media thickness and its progression over three years: a multicenter European study. Nutr Metab Cardiovasc Dis 2013;23:151–8.10.1016/j.numecd.2011.04.006Search in Google Scholar PubMed

26. Beer NL, Tribble ND, McCulloch LJ, Roos C, Johnson PR, Orho-Melander M, et 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;18:4081–8.10.1093/hmg/ddp357Search in Google Scholar PubMed PubMed Central

27. Rees MG, Ng D, Ruppert S, Turner C, Beer NL, Swift AJ, et al. Correlation of rare coding variants in the gene encoding human glucokinase regulatory protein with phenotypic, cellular, and kinetic outcomes. J Clin Invest 2012;122:205–17.10.1172/JCI46425Search in Google Scholar PubMed PubMed Central

28. Rees MG, Wincovitch S, Schultz J, Waterstradt R, Beer NL, Baltrusch S, et al. Cellular characterisation of the GCKR P446L variant associated with type 2 diabetes risk. Diabetologia 2012;55:114–22.10.1007/s00125-011-2348-5Search in Google Scholar PubMed PubMed Central

29. Agius L. High-carbohydrate diets induce hepatic insulin resistance to protect the liver from substrate overload. Biochem Pharmacol 2013;85:306–12.10.1016/j.bcp.2012.09.019Search in Google Scholar PubMed

Received: 2013-2-4
Accepted: 2013-8-4
Published Online: 2013-8-29
Published in Print: 2014-2-1

©2014 by Walter de Gruyter Berlin Boston

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