Email this article Associations between glucokinase and glucokinase regulatory protein gene polymorphisms and clinical parameters in pregnant women
Abstract
Introduction: Glucose is the main energy substrate for intrauterine growth. Changes in the metabolism of carbohydrates, the predominant dietary source of glucose, may adversely influence the foetus, for example resulting in large for gestational age infants. The uptake and storage of glucose is regulated by glucokinase (GCK), an enzyme modulated by the glucokinase regulatory protein (GCKR), which catalyses hepatic phosphorylation of glucose, leading to the synthesis of glycogen and triacylglycerols.
As the polymorphisms GCK rs1799884 and GCKR rs780094 have been implicated in dyslipidaemia and diabetes mellitus type 2 in pregnancy, the aim of this study was to examine the associations between these polymorphisms and clinical parameters in pregnant women.
Materials and methods: This study included 207 pregnant women with normal values of oral glucose tolerance test (OGTT). We analysed associations between the studied polymorphisms and clinical parameters, such as body mass before pregnancy, body mass at delivery, body mass increase during pregnancy, body mass index (BMI) before pregnancy, BMI at delivery, BMI increase during pregnancy, gestational age at delivery, newborn body mass, APGAR score and glucose concentrations in OGTT.
Results and conclusion: There were no statistically significant associations between the GCK rs1799884 and GCKR rs780094 polymorphisms and the studied clinical parameters apart from a higher BMI increase during pregnancy in women with the GCK rs1799884 CC genotype.
Keywords
Full Text:
PDFReferences
Bao W, Li S, Chavarro JE, Tobias DK, Zhu Y, Hu FB, et al. Low carbohydrate-diet scores and long-term risk of type 2 diabetes among women with a history of gestational diabetes mellitus: a prospective cohort study. Diabetes Care 2016;39(1):43-9. doi: 10.2337/dc15-1642.
Pang WW, Colega M, Cai S, Chan YH, Padmapriya N, Chen LW, et al. Higher maternal dietary protein intake is associated with a higher risk of gestational diabetes mellitus in a multi-ethnic Asian cohort. J Nutr 2017;147(4):653-60. doi: 10.3945/jn.116.243881.
Hoirisch-Clapauch S, Porto MA, Nardi AE. May maternal lifestyle have an impact on neonatal glucose levels? Med Hypotheses 2016;87:80-6. doi: 10.1016/j.mehy.2015.11.017.
Donnelly JM, Walsh JM, Byrne J, Molloy EJ, McAuliffe FM. Impact of maternal diet on neonatal anthropometry: a randomized controlled trial. Pediatr Obes 2015;10(1):52-6. doi: 10.1111/j.2047-6310.2013.00216.x.
Ahlsson F, Diderholm B, Jonsson B, Nordén-Lindberg S, Olsson R, Ewald U, et al. Insulin resistance, a link betweenvmaternal overweight and fetal macrosomia in nondiabetic pregnancies. Horm Res Paediatr 2010;74(4):267-74. doi: 10.1159/000295710.
Zheng J, Zhang Q, Mul JD, Yu M, Xu J, Qi C, et al. Maternal high-calorie diet is associated with altered hepatic microRNA expression and impaired metabolic health in offspring at weaning age. Endocrine 2016;54(1):70-80. doi: 10.1007/s12020-016-0959-9.
Markwardt ML, Seckinger KM, Rizzo MA. Regulation of glucokinase by intracellular calcium levels in pancreatic β cells. J Biol Chem 2016;291(6):3000-9. doi: 10.1074/jbc.M115.692160.
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. doi: 10.1186/1475-2840-9-79.
Hishida A, Morita E, Naito M, Okada R, Wakai K, Matsuo K, et al. Associations of apolipoprotein A5 (APOA5), glucokinase (GCK) and glucokinase regulatory protein (GCKR) polymorphisms and lifestyle factors with the risk of dyslipidemia and dysglycemia in Japanese – a cross-sectional data from the J-MICC Study. Endocr J 2012;59(7):589-99.
Fu D, Cong X, Ma Y, Cai H, Cai M, Li D, et al. Genetic polymorphism of glucokinase on the risk of type 2 diabetes and impaired glucose regulation: evidence based on 298,468 subjects. PLoS One 2013;8(2):e55727. doi: 10.1371/journal.pone.0055727.
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(1):70-5. doi: 10.1007/s00125-007-0865-z.
Agius L. Hormonal and metabolite regulation of hepatic glucokinase. Annu Rev Nutr 2016;36:389-415. doi: 10.1146/annurev-nutr-071715-051145.
Haeusler RA, Camastra S, Astiarraga B, Nannipieri M, Anselmino M, Ferrannini E. Decreased expression of hepatic glucokinase in type 2 diabetes. Mol Metab 2014;4(3):222-6. doi: 10.1016/j.molmet.2014.12.007.
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(21):4081-8. doi: 10.1093/hmg/ddp357.
Cullen KS, Al-Oanzi ZH, O’Harte FP, Agius L, Arden C. Glucagon induces translocation of glucokinase from the cytoplasm to the nucleus of hepatocytes by transfer between 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase-2 and the glucokinase regulatory protein. Biochim Biophys Acta 2014;1843(6):1123-34. doi: 10.1016/j.bbamcr.2014.02.006.
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(1):114-22. doi: 10.1007/s00125-011-2348-5.
Park JM, Kim TH, Jo SH, Kim MY, Ahn YH. Acetylation of glucokinase regulatory protein decreases glucose metabolism by suppressing glucokinase activity. Sci Rep 2015;5:17395. doi: 10.1038/srep17395.
Li X, Shu YH, Xiang AH, Trigo E, Kuusisto J, Hartiala J, et al. Additive effects of genetic variation in GCK and G6PC2 on insulin secretion and fasting glucose. Diabetes 2009;58(12):2946-53. doi: 10.2337/db09-0228.
Hu C, Zhang R, Wang C, Yu W, Lu J, Ma X, et al. Effects of GCK, GCKR, G6PC2 and MTNR1B variants on glucose metabolism and insulin secretion. PLoS One 2010;5(7):e11761. doi: 10.1371/journal.pone.0011761.
Tam CH, Ho JS, Wang Y, Lee HM, Lam VK, Germer S, et al. Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. PLoS One 2010;5(7):e11428. doi: 10.1371/journal.pone.0011428.
Han X, Cui H, Chen X, Xie W, Chang Y. Association of the glucokinase gene promoter polymorphism −30G > A (rs1799884) with gestational diabetes mellitus susceptibility: a case-control study and meta-analysis. Arch Gynecol Obstet 2015;292(2):291-8. doi: 10.1007/s00404-015-3635-z.
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(5):834-43. doi: 10.1007/s00125-009-1290-2.
Stuebe AM, Wise A, Nguyen T, Herring A, North KE, Siega-Riz AM. Maternal genotype and gestational diabetes. Am J Perinatol 2014;31(1):69-76. doi: 10.1055/s-0033-1334451.
Huopio H, Cederberg H, Vangipurapu J, Hakkarainen H, Pääkkönen M, Kuulasmaa T, et al. Association of risk variants for type 2 diabetes and hyperglycemia with gestational diabetes. Eur J Endocrinol 2013;169(3):291-7. doi: 10.1530/EJE-13-0286.
Zheng J, Xiao X, Zhang Q, Yu M, Xu J, Wang Z. Maternal protein restriction induces early-onset glucose intolerance and alters hepatic genes expression in the peroxisome proliferator-activated receptor pathway in offspring. J Diabetes Investig 2015;6(3):269-79. doi: 10.1111/jdi.12303.
Walsh JM, Mahony RM, Canty G, Foley ME, McAuliffe FM. Identification of those most likely to benefit from a low-glycaemic index dietary intervention in pregnancy. Br J Nutr 2014;112(4):583-9. doi: 10.1017/S000711451400110X.
DOI: https://doi.org/10.21164/pomjlifesci.440
Copyright (c) 2018
License URL: https://creativecommons.org/licenses/by-nc-nd/3.0/pl/