Enlightening the Correlation of Polymorphisms at FTO, LEP and LEPR Genes with Gestational Diabetes Mellitus Risk: a Meta-analysis

Document Type : Original Article

Authors

1 Department of Pediatrics, Islamic Azad University of Yazd, Yazd, Iran

2 Preventative Gynecology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

4 Neonatal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

5 Firoozgar Clinical Research Development Center (FCRDC), Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran

6 Department of Cancer Biology, College of Medicine, University of Cincinnati, Ohio, USA

7 Akbarabadi Clinical Research Development Unit, Iran University of Medical Sciences, Tehran, Iran

8 Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

9 Cellular and Molecular Biology Research Center, School of Medicine, Shahid Sadoughi Yazd University of Medical Sciences, Yazd, Iran

10 Mother and Newborn Health Research Center, Shahid Sadoughi Hospital, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Abstract

Background: The adverse outcomes correlated with GDM for both the mother and the offspring are diverse. The link between polymorphisms at fat mass and obesity‐correlated protein (FTO), leptin (LEP), and leptin receptor (LEPR) genes and GDM is ambiguous. In this meta-analysis, we sought to investigate the correlation of FTO, LEP, and LEPR polymorphisms with GDM risk.
Methods: We performed an online search on PubMed, Web of Science, and Google Scholar databases to identify all relevant research.
Results: A total of 18 case-control studies including seven research with 893 cases and 2875 controls on FTO rs9939609, four research with 1345 cases and 1116 controls on FTO rs8050136, two research with 207 cases and 205 controls on FTO rs1421085, three studies with 529 cases and 581 controls on LEP rs7799039, and two research with 480 cases and 477 controls on LPER rs1137101 met our criteria. Combined data illustrated that the FTO rs9939609 and rs8050136 were correlated with substantial risk of GDM in the overall population, but not FTO rs1421085. Furthermore, LEP rs2167270 and rs7799039 polymorphisms were not correlated with GDM risk. Sorted analyses illustrated that the FTO rs9939609 polymorphism was correlated with GDM in Caucasian women.
Conclusion: This meta-analysis results illustrated that the FTO rs9939609 and rs8050136 were correlated with substantial risk of GDM, but not FTO rs1421085, LEP rs7799039, and LPER rs1137101. Larger and more rigorous studies among different ethnicities are needed to further evaluate the correlations with GDM.

Keywords

Corresponding Author: Reza Bahrami
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References

  1. Kapur A, McIntyre HD, Divakar H, Di Renzo GC, Kihara AB, McAuliffe F, et al. Towards a global consensus on GDM diagnosis: Light at the end of the tunnel? International Journal of Gynecology & Obstetrics. 2020 Jun 25;149(3):257–61.
  2. Alfadhli EM. Gestational diabetes mellitus. Saudi Medical Journal. 2015;36(4):399–406.
  3. Valizadeh M, Hosseinpanah F, Ramezani Tehrani F, Abdi H, Mehran L, Hadaegh F, et al. Iranian Endocrine Society Guidelines for Screening, Diagnosis, and Management of Gestational Diabetes Mellitus. Int J Endocrinol Metab. 2020 Dec 23;19(1):e107906.
  4. Lee KW, Ching SM, Ramachandran V, Yee A, Hoo FK, Chia YC, et al. Prevalence and risk factors of gestational diabetes mellitus in Asia: A systematic review and meta-analysis. BMC Pregnancy and Childbirth. 2018 Dec 14;18(1):1–20.
  5. Asadi M, Shahzeidi M, Nadjarzadeh A, Hashemi Yusefabad H, Mansoori A. The relationship between pre‐pregnancy dietary patterns adherence and risk of gestational diabetes mellitus in Iran: A case–control study. Nutrition & Dietetics. 2019 Nov 6;76(5):597–603.
  6. Elliott HR, Sharp GC, Relton CL, Lawlor DA. Epigenetics and gestational diabetes: a review of epigenetic epidemiology studies and their use to explore epigenetic mediation and improve prediction. Diabetologia. 2019 Dec 1;62(12):2171–8.
  7. Haertle L, El Hajj N, Dittrich M, Müller T, Nanda I, Lehnen H, et al. Epigenetic signatures of gestational diabetes mellitus on cord blood methylation. Clinical Epigenetics. 2017 Mar 27;9(1):28.
  8. Franzago M, Fraticelli F, Stuppia L, Vitacolonna E. Nutrigenetics, epigenetics and gestational diabetes: consequences in mother and child. Epigenetics. 2019 Mar 4;14(3):215–35.
  9. Amini K, Vakili Ogharood M, Davari M, Ershadifard S, Asadi H. A Case of A Fractured Fragment of Tracheostomy Tube Entering the Left Bronchus: A Case Report. J Babol Univ Med Sci. 2021;23(1):393–7.
  10. Hasanpour Dargah M, Samadi N, Vakili J, Isazadefar K, Kebar SM, Zade ARM, et al. Comparative analysis of the effects of vasoperssin and norepinephrine on the renal function in patients undergoing CABG; A randomized clinical trial. Iranian Red Crescent Medical Journal [Internet]. 2018 Aug 1;20(8):e67026.
  11. Lawrence RL, Wall CR, Bloomfield FH. Prevalence of gestational diabetes according to commonly used data sources: An observational study. BMC Pregnancy and Childbirth. 2019 Oct 11;19(1):349.
  12. Rosik J, Szostak B, Machaj F, Pawlik A. The role of genetics and epigenetics in the pathogenesis of gestational diabetes mellitus. Annals of Human Genetics. 2020 Mar 1;84(2):114–24.
  13. Amini M, Kazemnejad A, Zayeri F, Montazeri A, Rasekhi A, Amirian A, et al. Diagnostic accuracy of maternal serum multiple marker screening for early detection of gestational diabetes mellitus in the absence of a gold standard test. BMC Pregnancy and Childbirth. 2020 Jun 26;20(1):375.
  14. Dobjanschi C, Miulescu RD. Risk Factors For Gestational Diabetes - An Update. Romanian Journal of Diabetes, Nutrition and Metabolic Diseases [Internet]. 2015 Jun 1;22(2):201–7.
  15. Melchior H, Kurch-Bek D, Mund M. The Prevalence of Gestational Diabetes: A Population-Based Analysis of a Nationwide Screening Program. Deutsches Arzteblatt International. 2017 Jun 16;114(24):412–8.
  16. Nguyen CL, Pham NM, Binns CW, Van Duong D, Lee AH. Prevalence of gestational diabetes mellitus in eastern and southeastern Asia: A systematic review and meta-analysis. Vol. 2018, Journal of Diabetes Research. Hindawi Limited; 2018.
  17. Muche AA, Olayemi OO, Gete YK. Effects of gestational diabetes mellitus on risk of adverse maternal outcomes: A prospective cohort study in Northwest Ethiopia. BMC Pregnancy and Childbirth. 2020 Feb 3;20(1):73.
  18. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The pathophysiology of gestational diabetes mellitus. International Journal of Molecular Sciences. 2018 Nov 1;19(11).
  19. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013 Jan;36(SUPPL.1):S67-74.
  20. Yahaya TO, Salisu T, Abdulrahman YB, Umar AK. Update on the genetic and epigenetic etiology of gestational diabetes mellitus: a review. Egyptian Journal of Medical Human Genetics [Internet]. 2020;21(1):1–13.
  21. Pawlik A, Teler J, Maciejewska A, Sawczuk M, Safranow K, Dziedziejko V. Adiponectin and leptin gene polymorphisms in women with gestational diabetes mellitus. Journal of Assisted Reproduction and Genetics. 2017 Apr 1;34(4):511–6.
  22. Deng X, Su R, Stanford S, Chen J. Critical Enzymatic Functions of FTO in Obesity and Cancer. Frontiers in Endocrinology. 2018 Jul 30;9:396.
  23. Peters U, North KE, Sethupathy P, Buyske S, Haessler J, Jiao S, et al. A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study. PLoS Genetics. 2013 Jan;9(1):0.
  24. Peters U, Bien S, Zubair N. Genetic architecture of colorectal cancer. Gut. 2015 Oct 1;64(10):1623–36.
  25. Peng S, Zhu Y, Xu F, Ren X, Li X, Lai M. FTO gene polymorphisms and obesity risk: A meta-analysis. BMC Medicine. 2011 Jun 8;9(1):71.
  26. Dastgheib SA, Bahrami R, Setayesh S, Salari S, Mirjalili SR, Noorishadkam M, et al. Evidence from a meta-analysis for association of MC4R rs17782313 and FTO rs9939609 polymorphisms with susceptibility to obesity in children. Diabetes Metab Syndr [Internet]. 2021 Sep 1;15(5):102234.
  27. Jafari-Nedooshan J, Kargar S, Neamatzadeh H, Haghighi F, Dehghani Mohammad Abadi R, Seddighi N. Lack of Association of the Fat Mass and Obesity Associated (FTO) Gene rs9939609 Polymorphism with Breast Cancer Risk: a Systematic Review and Meta-Analysis Based on Case - Control Studies. Asian Pac J Cancer Prev. 2017;18(4):1031–7.
  28. Al-Serri A, Alroughani R, Al-Temaimi RA. The FTO gene polymorphism rs9939609 is associated with obesity and disability in multiple sclerosis patients. Scientific Reports. 2019 Dec 1;9(1):1–6.
  29. Mozafarizadeh M, Omran SP, Kordestani Z, Dehghan HM, Faridazar A, Houshmand M. Association of obesity-related genetic variants (FTO and MC4R) with breast cancer risk: A population-based case–control study in Iran. Iranian Journal of Biotechnology. 2019 Sep 1;17(4):25–30.
  30. Kaklamani V, Yi N, Sadim M, Siziopikou K, Zhang K, Xu Y, et al. The role of the fat mass and obesity associated gene (FTO) in breast cancer risk. BMC Medical Genetics. 2011 Apr 13;12(1):52.
  31. Tarnowski M, Bujak J, Kopytko P, Majcher S, Ustianowski P, Dziedziejko V, et al. Effect of FTO and IGF2BP2 gene polymorphisms on duration of pregnancy and Apgar scores in women with gestational diabetes. Journal of Obstetrics and Gynaecology. 2019 Feb 17;39(2):151–6.
  32. Paracchini V, Pedotti P, Taioli E. Genetics of Leptin and Obesity: A HuGE Review. American Journal of Epidemiology. 2005 Jul 15;162(2):101–14.
  33. Li YY, Wang H, Yang XX, Wu JJ, Geng HY, Kim HJ, et al. LEPR gene Gln223Arg polymorphism and type 2 diabetes mellitus: A meta-analysis of 3,367 subjects. Oncotarget. 2017 Sep 1;8(37):61927–34.
  34. Collares RVA, Salgado W, Da Cunha Tirapelli DP, Dos Santos JS. The expression of LEP, LEPR, IGF1 and IL10 in obesity and the relationship with microRNAs. PLoS ONE. 2014 Apr 1;9(4).
  35. Yang M, Peng S, Li W, Wan Z, Fan L, Du Y. Relationships between plasma leptin levels, leptin G2548A, leptin receptor Gln223Arg polymorphisms and gestational diabetes mellitus in Chinese population. Scientific Reports. 2016 Apr 1;6:23948.
  36. Lauenborg J, Grarup N, Damm P, Borch-Johnsen K, Jørgensen T, Pedersen O, et al. Common Type 2 Diabetes Risk Gene Variants Associate with Gestational Diabetes. The Journal of Clinical Endocrinology & Metabolism. 2009 Jan 1;94(1):145–50.
  37. Cho YM, Kim TH, Lim S, Choi SH, Shin HD, Lee HK, et al. Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population. Diabetologia. 2009 Feb 11;52(2):253–61.
  38. Vakili Ojarood M, Khanghah AS, Belalzadeh M. Gangrenous Ischemic Colitis Due to Acute Promyelocytic Leukaemia, and Myelofibrosis in a 62-year-old Man Suffering from ESRD; Case Report. Int J Surg Case Rep. 2021 Dec 1;89(2021):106663.
  39. Shirinzadeh-Dastgiri A, Saberi A, Vakili M, Marashi SM. 21-Year-Old Female with Pneumothorax and Massive Air Leak Following Blunt Trauma; a Photo Quiz. Arch Acad Emerg Med [Internet]. 2022;10(1):e24.
  40. Ling X, Junjun S, Dan G. A study of the correlation between single nucleotide polymorphism of FTO gene rs9939609 and the risk of gestational diabetes mellitus. China Modern Doctor. 2020;20:10–3.
  41. Davari H, Rahim MB, Ershadi R, Rafieian S, Mardani P, Vakili MR, et al. First Iranian Experience of the Minimally Invasive Nuss Procedure for Pectus Excavatum Repair: A Case Series and Literature Review. Iranian Journal of Medical Sciences. 2018 Sep 1;43(5):554–9.
  42. Anghebem-Oliveira MI, Martins BR, Alberton D, de Souza Ramos EA, Picheth G, Rego FG de M. Type 2 diabetes-associated genetic variants of FTO, LEPR, PPARg, and TCF7l2 in gestational diabetes in a Brazilian population. Archives of Endocrinology and Metabolism [Internet]. 2017;61(3):238–48.
  43. Teleginski A, Welter M, Frigeri HR, Réa RR, Souza EM, Alberton D, et al. Leptin (rs7799039) and solute carrier family 30 zinc transporter (rs13266634) polymorphisms in Euro-Brazilian pregnant women with gestational diabetes. Genetics and Molecular Research. 2017 Mar 30;16(1).
  44. Beysel S, Eyerci N, Ulubay M, Caliskan M, Kizilgul M, Haflzoǧlu M, et al. Maternal genetic contribution to pre-pregnancy obesity, gestational weight gain, and gestational diabetes mellitus. Diabetology and Metabolic Syndrome. 2019 May 14;11(1).
  45. Saucedo R, Valencia J, Gutierrez C, Basurto L, Hernandez M, Puello E, et al. Gene variants in the FTO gene are associated with adiponectin and TNF-alpha levels in gestational diabetes mellitus. Diabetology and Metabolic Syndrome. 2017 May 12;9(1).
  46. Franzago M, Fraticelli F, Nicolucci A, Celentano C, Liberati M, Stuppia L, et al. Molecular Analysis of a Genetic Variants Panel Related to Nutrients and Metabolism: Association with Susceptibility to Gestational Diabetes and Cardiometabolic Risk in Affected Women. Journal of Diabetes Research. 2017;2017:4612623.
  47. de Melo SF, Frigeri HR, dos Santos-Weiss ICR, Réa RR, de Souza EM, Alberton D, et al. Polymorphisms in FTO and TCF7L2 genes of Euro-Brazilian women with gestational diabetes. Clinical Biochemistry [Internet]. 2015 Nov 1;48(16–17):1064–7.
  48. Pagán A, Sabater-Molina M, Olza J, Prieto-Sánchez MT, Blanco-Carnero JE, Parrilla JJ, et al. A gene variant in the transcription factor 7-like 2 (TCF7L2) is associated with an increased risk of gestational diabetes mellitus. European Journal of Obstetrics and Gynecology and Reproductive Biology [Internet]. 2014 Sep 1;180(1):77–82.
  49. Vaškú JAB, Vaškú A, Dostálová Z, Bienert P. Association of leptin genetic polymorphism -2548 G/A with gestational diabetes mellitus. Genes & Nutrition [Internet]. 2006 Jun;1(2):117–23.
  50. Nasiri-Amiri F, Sepidarkish M, Shirvani MA, Habibipour P, Tabari NSM. The effect of exercise on the prevention of gestational diabetes in obese and overweight pregnant women: A systematic review and meta-Analysis. Diabetology and Metabolic Syndrome. 2019 Aug 27;11(1):72.
  51. Shaat N, Lernmark Å, Karlsson E, Ivarsson S, Parikh H, Berntorp K, et al. A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus. Diabetologia. 2007 May 7;50(5):972–9.
  52. Guo F, Long W, Zhou W, Zhang B, Liu J, Yu B. FTO, GCKR, CDKAL1 and CDKN2A/B gene polymorphisms and the risk of gestational diabetes mellitus: a meta-analysis. Archives of Gynecology and Obstetrics. 2018 Oct 1;298(4):705–15.
  53. Kalantari N, Doaei S, Keshavarz-Mohammadi N, Gholamalizadeh M, Pazan N. Review of studies on the fat mass and obesity-associated (FTO) gene interactions with environmental factors affecting on obesity and its impact on lifestyle interventions. ARYA Atherosclerosis. 2016;12(6):281–90.
  54. Fawcett KA, Barroso I. The genetics of obesity: FTO leads the way. Trends in Genetics. 2010 Jun;26(6):266–74.
  55. He H, Cao W ting, Zeng Y hui, Huang Z qing, Du W rong, Guan N di, et al. Lack of associations between the FTO polymorphisms and gestational diabetes: A meta-analysis and trial sequential analysis. Gene [Internet]. 2018 Nov 30;677:169–75.
  56. Lin Z, Wang Y, Zhang B, Jin Z. Association of type 2 diabetes susceptible genes GCKR, SLC30A8, and FTO polymorphisms with gestational diabetes mellitus risk: a meta-analysis. Endocrine. 2018 Oct 1;62(1):34–45.
  57. Henson MC, Castracane VD. Leptin in pregnancy: An update. Biology of Reproduction. 2006 Feb 1;74(2):218–29.
World Journal of Peri and Neonatology
Volume 6, Issue 1
December 2023
Pages 26-39

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History

  • Receive Date: 07 December 2023
  • Accept Date: 07 December 2023
  • First Publish Date: 07 December 2023

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