Journal Mobile Options
Table of Contents
Vol. 76, No. 4, 2013
Issue release date: November 2013
Gynecol Obstet Invest 2013;76:221-227

Association between Genetic Variations in MTNR1A and MTNR1B Genes and Gestational Diabetes Mellitus in Han Chinese Women

Li C. · Qiao B. · Zhan Y. · Peng W. · Chen Z.-J. · Sun L. · Zhang J. · Zhao L. · Gao Q.
Departments of aObstetrics, bPediatrics and cGynecology, The Affiliated Hospital of Medical College, Qingdao University, dDepartment of Radiology, Qingdao Municipal Hospital, Qingdao, and eShandong Provincial Key Laboratory of Reproductive Medicine, Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background/Aims: The purpose of this study was to investigate the association between MTNR1A and MTNR1B gene polymorphisms and gestational diabetes mellitus (GDM) in Han Chinese women. Methods: Study participants included 350 patients with GDM and 480 control subjects. Three single-nucleotide polymorphisms (SNPs; rs2119882 in MTNR1A and rs10830963 and rs10830962 in MTNR1B) were genotyped using direct sequencing. Genotype and allele distributions of SNPs in cases of GDM and controls were analyzed. Association of the MTNR1A and MTNR1B gene variants with plasma glucose and insulin levels as well as blood lipid levels was further investigated. Results: The frequencies of genotypes and allele types of rs2119882 in MTNR1A and rs10830963 in MTNR1B were significantly different between women with GDM and controls (p < 0.05). Moreover, in the GDM group, these SNPs were associated with increased fasting plasma glucose concentrations (p < 0.001) and increased homeostasis model assessment of insulin resistance (p < 0.001). The rs10830962 polymorphism in MTNR1B was not associated with an increased risk of developing GDM or any of the clinical or metabolic characteristics in patients with GDM (p > 0.05). Conclusion: The genetic polymorphisms rs2119882 in MTNR1A and rs10830963 in MTNR1B are associated with an increased risk of developing GDM and insulin resistance in Han Chinese women. © 2013 S. Karger AG, Basel

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Metzger BE: Summary and recommendations of the Third International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes 1991;40:197-201.
  2. Shaat N, Groop L: Genetics of gestational diabetes mellitus. Curr Med Chem 2007;14:569-583.
  3. Ferrara A, Kahn HS, Quesenberry CP, Riley C, Hedderson MM: An increase in the incidence of gestational diabetes mellitus: Northern California, 1991-2000. Obstet Gynecol 2004;103:526-533.
  4. Dabelea D, Snell-Bergeon JK, Hartsfield CL, Bischoff KJ, Hamman RF, McDuffie RS: Increasing prevalence of gestational diabetes mellitus (GDM) over time and by birth cohort: Kaiser Permanente of Colorado GDM Screening Program. Diabetes Care 2005;28:579-584.
  5. Tam W-H, Ma RC, Yang X, Ko GT, Lao TT, Chan MH, Lam CW, Cockram CS, Chan JC: Cardiometabolic risk in Chinese women with prior gestational diabetes: a 15-year follow-up study. Gynecol Obstet Invest 2012;73:168-176.
  6. Buchanan TA, Xiang AH: Gestational diabetes mellitus. J Clin Invest 2005;115:485-491.
  7. Saucedo R, Zarate A, Basurto L, Hernandez M, Puello E, Campos S, Moreno E: Women with gestational diabetes develop glucose intolerance with high frequency within one year postpartum. Gynecol Obstet Invest 2012;73:58-62.
  8. Linné Y, Barkeling B, Rössner S: Natural course of gestational diabetes mellitus: long term follow up of women in the SPAWN study. BJOG 2002;109:1227-1231.
  9. Williams MA, Qiu C, Dempsey JC, Luthy DA: Familial aggregation of type 2 diabetes and chronic hypertension in women with gestational diabetes mellitus. J Reprod Med 2003;48:955-962.

    External Resources

  10. Stumpf I, Muhlbauer E, Peschke E: Involvement of the cGMP pathway in mediating the insulin-inhibitory effect of melatonin in pancreatic beta-cells. J Pineal Res 2008;45:318-327.
  11. Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, Laposky A, Losee-Olson S, Easton A, Jensen DR, Eckel RH, Takahashi JS, Bass J: Obesity and metabolic syndrome in circadian clock mutant mice. Science 2005;308:1043-1045.
  12. Spiegel K, Leproult R, Van Cauter E: Impact of sleep debt on metabolic and endocrine function. Lancet 1999;354:1435-1439.
  13. Ramracheya RD, Muller DS, Squires PE, Brereton H, Sugden D, Huang GC, Amiel SA, Jones PM, Persaud SJ: Function and expression of melatonin receptors on human pancreatic islets. J Pineal Res 2008;44:273-279.
  14. Von Gall C, Stehle JH, Weaver DR: Mammalian melatonin receptors: molecular biology and signal transduction. Cell Tissue Res 2002;309:151-162.
  15. Morcuende JA, Minhas R, Dolan L, Stevens J, Beck J, Wang K, Weinstein SL, Sheffield V: Allelic variants of human melatonin 1A receptor in patients with familial adolescent idiopathic scoliosis. Spine 2003;28:2025-2029.
  16. Rönn T, Wen J, Yang Z, Lu B, Du Y, Groop L, Hu R, Ling C: A common variant in MTNR1B, encoding melatonin receptor 1B, is associated with type 2 diabetes and fasting plasma glucose in Han Chinese individuals. Diabetologia 2009;52:830-833.
  17. Lyssenko V, Nagorny CL, Erdos MR, Wierup N, Jonsson A, Spégel P, Bugliani M, Saxena R, Fex M, Pulizzi N, Isomaa B, Tuomi T, Nilsson P, Kuusisto J, Tuomilehto J, Boehnke M, Altshuler D, Sundler F, Eriksson JG, Jackson AU, Laakso M, Marchetti P, Watanabe RM, Mulder H, Groop L: Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat Genet 2009;41:82-88.
  18. Staiger H, Machicao F, Schäfer SA, Kirchhoff K, Kantartzis K, Guthoff M, Silbernagel G, Stefan N, Häring H-U, Fritsche A: Polymorphisms within the novel type 2 diabetes risk locus MTNR1B determine β-cell function. PLoS One 2008;3:e3962.
  19. Wang Y, Nie M, Li W, Ping F, Hu Y, Ma L, Gao J, Liu J: Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population. PLoS One 2011;6:e26953.
  20. Kim JY, Cheong HS, Park BL, Baik SH, Park S, Lee SW, Kim MH, Chung JH, Choi JS, Kim MY, Yang JH, Cho DH, Shin HD, Kim SH: Melatonin receptor 1B polymorphisms associated with the risk of gestational diabetes mellitus. BMC Med Genet 2011;12:82.
  21. Kwak SH, Jang HC, Park KS: Finding genetic risk factors of gestational diabetes. Genomics Inform 2012;10:239-243.
  22. Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005;21:263-265.
  23. Boden G, Ruiz J, Urbain JL, Chen X: Evidence for a circadian rhythm of insulin secretion. Am J Physiol 1996;271:246-252.

    External Resources

  24. Jaworek J, Nawrot-Porabka K, Leja-Szpak A, Bonior J, Szklarczyk J, Kot M, Konturek SJ, Pawlik WW: Melatonin as modulator of pancreatic enzyme secretion and pancreatoprotector. J Physiol Pharmacol 2007;58:65-80.

    External Resources

  25. Adriaens I, Jacquet P, Cortvrindt R, Janssen K, Smitz J: Melatonin has dose-dependent effects on folliculogenesis, oocyte maturation capacity and steroidogenesis. Toxicology 2006;228:333-343.
  26. Park HJ, Park JK, Kim SK, Cho A-R, Kim JW, Yim S-V, Chung J-H: Association of polymorphism in the promoter of the melatonin receptor 1A gene with schizophrenia and with insomnia symptoms in schizophrenia patients. J Mol Neurosci 2011;45:304-308.
  27. Vlassi M, Gazouli M, Paltoglou G, Christopoulos P, Florentin L, Kassi G, Mastorakos G: The rs10830963 variant of melatonin receptor MTNR1B is associated with increased risk for gestational diabetes mellitus in a Greek population. Hormones 2012;11:70-76.

    External Resources

  28. Li C, Shi Y, You L, Wang L, Chen Z-J: Melatonin receptor 1A gene polymorphism associated with polycystic ovary syndrome. Gynecol Obstet Invest 2011;72:130-134.
  29. Li C, Shi Y, You L, Wang L, Chen Z-J: Association of rs10830963 and rs10830962 SNPs in the melatonin receptor (MTNR1B) gene among Han Chinese women with polycystic ovary syndrome. Mol Hum Reprod 2011;17:193-198.
  30. Pandi-Perumal SR, Trakht I, Spence DW, Srinivasan V, Dagan Y, Cardinali DP: Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol 2008;85:335-353.
  31. Dubocovich ML: Melatonin receptors: are there multiple subtypes? Trends Pharmacol Sci 1995;16:50-56.
  32. Reppert SM, Weaver DR, Ebisawa T: Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron 1994;13:1177-1185.
  33. Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF: Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc Natl Acad Sci USA 1995;92:8734-8738.
  34. Liao S, Liu Y, Tan Y, Gan L, Mei J, Song W, Chi S, Dong X, Chen X, Deng S: Association of genetic variants of melatonin receptor 1B with gestational plasma glucose level and risk of glucose intolerance in pregnant Chinese women. PLoS One 2012;7:e40113.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50