Skip to main content
SpringerLink
Log in

Genetic determinants of gestational diabetes mellitus: a case–control study in two independent populations

  • Original Article
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

Background

Genetic risk score (GRS) is more informative to identify the complicated associations between variants of genes and disease. Considering similar pathogenesis and shared genetic predispositions between gestational diabetes mellitus (GDM) and type 2 diabetes/obesity, we conducted this study to explore whether the GRS model integrating variants related to type 2 diabetes/obesity is also associated with GDM risk.

Methods

A population-based case–control study that included 1429 subjects was conducted to investigate the association between the GRS model and GDM risk, which were analyzed employing stratified logistic regression analysis with the adjustment for age, BMI, parity and family history of diabetes.

Results

We have screened 23 SNPs and further filtered six SNPs that were significantly associated with the risk of GDM: four risk SNPs (MTNR1B: rs10830963, rs1387153, rs2166706; MC4R: rs2229616) and two protective SNPs (MTNR1B: rs1447352 and rs4753426). The GRS model with a higher score indicated a higher genetic predisposition to develop GDM, especially in the highest quartile of GRS (all P < 0.001) and the strata of advanced maternal age (all P < 0.001) and obesity (all P = 0.005).

Conclusion

In this study, six SNPs were explored and further identified to be associated with GDM risk, which suggested GRSs including these polymorphisms might participate in facilitating GDM risk. These findings offer the potential to improve our understanding of the etiology of GDM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The datasets generated during the current study are not publicly available due to local legislation, but are partially available from the corresponding author on reasonable request (Email: j_meili@126.com).

References

  1. American Diabetes A (2017) Classification and diagnosis of diabetes. Diabet Care 40(Suppl 1):S11–S24. https://doi.org/10.2337/dc17-S005

    Article  Google Scholar 

  2. Xie K, Chen T, Zhang Y, et al. (2019) Association of rs10830962 polymorphism with gestational diabetes mellitus risk in a Chinese population. Sci Rep 9(1):5357. https://doi.org/10.1038/s41598-019-41605-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kampmann U, Madsen LR, Skajaa GO, Iversen DS, Moeller N, Ovesen P (2015) Gestational diabetes: a clinical update. World J Diabet 6(8):1065–1072. https://doi.org/10.4239/wjd.v6.i8.1065

    Article  Google Scholar 

  4. Zhang C, Rawal S, Chong YS (2016) Risk factors for gestational diabetes: is prevention possible? Diabetologia 59(7):1385–1390. https://doi.org/10.1007/s00125-016-3979-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Franzago M, Fraticelli F, Stuppia L, Vitacolonna E (2019) Nutrigenetics, epigenetics and gestational diabetes: consequences in mother and child. Epigenetics 14(3):215–235. https://doi.org/10.1080/15592294.2019.1582277

    Article  PubMed  PubMed Central  Google Scholar 

  6. Watanabe RM (2011) Inherited destiny? Genetics and gestational diabetes mellitus. Genome Med 3(3):18. https://doi.org/10.1186/gm232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhang C, Bao W, Rong Y, et al. (2013) Genetic variants and the risk of gestational diabetes mellitus: a systematic review. Hum Reprod Update 19(4):376–390. https://doi.org/10.1093/humupd/dmt013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wu NN, Zhao D, Ma W, et al. (2019) A genome-wide association study of gestational diabetes mellitus in Chinese women. J Matern Fetal Neonatal Med. https://doi.org/10.1080/14767058.2019.1640205

    Article  PubMed  Google Scholar 

  9. Kawai VK, Levinson RT, Adefurin A, et al. (2017) A genetic risk score that includes common type 2 diabetes risk variants is associated with gestational diabetes. Clin Endocrinol (Oxf) 87(2):149–155. https://doi.org/10.1111/cen.13356

    Article  CAS  Google Scholar 

  10. Powe CENM, Talbot O, Allard C, et al. (2018) Genetic determinants of glycemic traits and the risk of gestational diabetes mellitus. Diabetes 67(12):2703–2709

    Article  Google Scholar 

  11. Ding M, Chavarro J, Olsen S, et al. (2018) Genetic variants of gestational diabetes mellitus: a study of 112 SNPs among 8722 women in two independent populations. Diabetologia 61(8):1758–1768. https://doi.org/10.1007/s00125-018-4637-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wei YM, Liu XY, Shou C, et al. (2019) Value of fasting plasma glucose to screen gestational diabetes mellitus before the 24th gestational week in women with different pre-pregnancy body mass index. Chin Med J (Engl) 132(8):883–888. https://doi.org/10.1097/CM9.0000000000000158

    Article  Google Scholar 

  13. Kim JY, Cheong HS, Park B-L, et al. (2011) Melatonin receptor 1 B polymorphisms associated with the risk of gestational diabetes mellitus. BMC Med Genet 12(1):82

    Article  CAS  Google Scholar 

  14. Kwak S-HK, Cho YM, Go MJ, et al. (2012) A genome-wide association study of gestational diabetes mellitus in Korean women. Diabetes 61(2):531–541. https://doi.org/10.2337/db11-1034/-/DC1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mao H, Li Q, Gao S (2012) Meta-analysis of the relationship between common type 2 diabetes risk gene variants with gestational diabetes mellitus. PLoS ONE 7(9):e45882. https://doi.org/10.1371/journal.pone.0045882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Huopio H, Cederberg H, Vangipurapu J, et al. (2013) Association of risk variants for type 2 diabetes and hyperglycemia with gestational diabetes. Eur J Endocrinol 169(3):291–297. https://doi.org/10.1530/EJE-13-0286

    Article  CAS  PubMed  Google Scholar 

  17. Ren J, Xiang AH, Trigo E, et al. (2014) Genetic variation in MTNR1B is associated with gestational diabetes mellitus and contributes only to the absolute level of beta cell compensation in Mexican Americans. Diabetologia 57(7):1391–1399. https://doi.org/10.1007/s00125-014-3239-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Stuebe AM, Wise A, Nguyen T, Herring A, North KE, Siega-Riz AM (2014) Maternal genotype and gestational diabetes. Am J Perinatol 31(1):69–76. https://doi.org/10.1055/s-0033-1334451

    Article  PubMed  Google Scholar 

  19. Li C, Zhou Y, Qiao B, Xu L, Li Y, Li C (2018) Association between a melatonin receptor 1B genetic polymorphism and its protein expression in gestational diabetes mellitus. Reprod Sci. https://doi.org/10.1177/1933719118765983

    Article  PubMed  PubMed Central  Google Scholar 

  20. Polina V, Popova AAK, Vasilyeva LB, et al. (2017) Effect of gene-lifestyle interaction on gestational diabetes risk. Oncotarget 8(67):112024

    Article  Google Scholar 

  21. Ramos E, Chen G, Shriner D, et al. (2011) Replication of genome-wide association studies (GWAS) loci for fasting plasma glucose in African–Americans. Diabetologia 54(4):783–788. https://doi.org/10.1007/s00125-010-2002-7

    Article  CAS  PubMed  Google Scholar 

  22. Liao S, Liu Y, Tan Y, et al. (2012) Association of genetic variants of melatonin receptor 1B with gestational plasma glucose level and risk of glucose intolerance in pregnant Chinese women. PLoS ONE 7(7):e40113. https://doi.org/10.1371/journal.pone.0040113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Salman M, Dasgupta S, Cholendra A, et al. (2015) MTNR1B gene polymorphisms and susceptibility to type 2 diabetes: a pilot study in South Indians. Gene 566(2):189–193. https://doi.org/10.1016/j.gene.2015.04.064

    Article  CAS  PubMed  Google Scholar 

  24. Zhan Y, Li C, Gao Q, Chen J, Yu S, Liu SG (2015) Association between the rs4753426 polymorphism in MTNR1B with fasting plasma glucose level and pancreatic beta-cell function in gestational diabetes mellitus. Genet Mol Res 14(3):8778–8785. https://doi.org/10.4238/2015.August.3.1

    Article  CAS  PubMed  Google Scholar 

  25. Tarnowski M, Malinowski D, Safranow K, Dziedziejko V, Pawlik A (2017) MTNR1A and MTNR1B gene polymorphisms in women with gestational diabetes. Gynecol Endocrinol 33(5):395–398. https://doi.org/10.1080/09513590.2016.1276556

    Article  CAS  PubMed  Google Scholar 

  26. Cormier H, Vigneault J, Garneau V, et al. (2015) An explained variance-based genetic risk score associated with gestational diabetes antecedent and with progression to pre-diabetes and type 2 diabetes: a cohort study. BJOG 122(3):411–419. https://doi.org/10.1111/1471-0528.12937

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We wish to thank Ying Chen, Department of Epidemiology and biostatistics, Nantong University, for his suggestions on the manuscript.

Funding

This study was supported by the Shanghai Municipal Health Commission (201840297) and supported by Shanghai Municipal Education Commission-Plateau Disciplinary Program for Medical Technology of SUMHS (2018–2020).

Author information

Author notes

  1. Yi Shen and Yulong Jia contributed equally to the paper.

Authors and Affiliations

  1. Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu Province, People’s Republic of China

    Yi Shen & Yulong Jia

  2. School of Management, Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China

    Yuandong Li

  3. Shanghai Key Laboratory for Molecular Imaging, University of Medicine and Health Sciences, Shanghai, People’s Republic of China

    Xuefeng Gu, Guoqing Wan & Liying Jiang

  4. School of Clinical Medicine, University of Medicine and Health Sciences, Shanghai, People’s Republic of China

    Peng Zhang

  5. Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu Province, People’s Republic of China

    Yafeng Zhang

Authors
  1. Yi Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yulong Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuandong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xuefeng Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guoqing Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yafeng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Liying Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YS and YLJ were responsible for the acquisition of data, analysis and interpretation of the data and drafting of the manuscript. YDL, XFG and GQW participated in the data collection and revision of the manuscript. PZ and SFZ analyzed and interpreted the data and revised the manuscript. LYJ contributed to the interpretation of results and made critical revisions. All authors have reviewed the final version of the manuscript and approved it for publication. LYJ is responsible for the integrity of the data.

Corresponding authors

Correspondence to Yafeng Zhang or Liying Jiang.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest associated with this manuscript.

Ethical approval

The study was approved by the Ethics Committee of Nantong University and carried out in accordance with the 1964 Helsinki declaration and its later amendments and comparable ethical standards.

Informed consent

Informed consent was obtained from all participants included in the study in a written way.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Liying Jiang and Yafeng Zhang joined directly to the paper.

This article belongs to the topical collection Pregnancy and Diabetes, managed by Antonio Secchi and Marina Scavini.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 19 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shen, Y., Jia, Y., Li, Y. et al. Genetic determinants of gestational diabetes mellitus: a case–control study in two independent populations. Acta Diabetol 57, 843–852 (2020). https://doi.org/10.1007/s00592-020-01485-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-020-01485-w

Keywords

Search

Navigation