The association between clock gene polymorphisms and type 2 diabetes: A systematic review and meta-analysis

Diabetes & Metabolic Syndrome Clinical Research & Reviews, vol. 19, pp. 103284

Abstract

BACKGROUND: Misalignment of the endogenous circadian system may contribute to the risk of type 2 diabetes. This systematic review and meta-analysis examined the association between clock gene polymorphisms and glycemic parameters and type 2 diabetes. METHODS: Embase, Medline, and Web of Science databases were searched from inception to August 20, 2024. Empirical studies examining the association between core clock gene polymorphisms and type 2 diabetes and glycemic parameters, and studies examining non-core clock genes with information on environmental factors were included. A multi-level meta-analytical approach was used, and a weighted odds ratio was reported (PROSPERO, CRD42022337706). RESULTS: In total, 37 studies comprising 535,063 participants were included. CRY2 was associated with higher fasting blood glucose (OR: 1.07, 95 % CI: 1.03-1.11) and impaired glucose tolerance (OR: 1.02, CI: 1.00-1.04). Polymorphisms in MTNR1B were associated with a greater risk of type 2 diabetes. CLOCK was associated with lower risk of type 2 diabetes (OR: 0.94, CI: 0.89-1.00), and PER3 was associated with lower fasting insulin (OR: 0.94, CI: 0.91-0.97) and lower risk of insulin resistance (OR: 0.92, CI: 0.88-0.95). These associations reflect pooled variant-level effects within genes, and the effects of certain variants were modified by diet, alcohol consumption, physical activity, sleep, and length of daylight. CONCLUSIONS: Specific polymorphisms in circadian genes, including CRY2, MTNR1B, CLOCK, and PER3, were associated with glycemic parameters and type 2 diabetes risk. These associations may be influenced by lifestyle and environmental factors, and interventions targeting circadian alignment could potentially modify diabetes risk, although further research is needed.

Authors 16

1. Divya Joshi

   McMaster University

   Affiliation as printed

   Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada

2. Marie Pigeyre

   McMaster University

   Affiliation as printed

   Department of Medicine, McMaster University, Hamilton, Ontario, Canada

3. Muhammad Usman Ali

   McMaster University

   Affiliation as printed

   Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada

4. Renée de Mutsert Aachen Department of Clinical Epidemiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, South Holland, the Netherlands

5. Femke Rutters

   Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Department of Epidemiology and Data Science, Amsterdam University Medical Centre, Location Vrije Universiteit Amsterdam, Amsterdam, North Holland, the Netherlands

6. David J.T. Campbell

   University of Calgary

   Affiliation as printed

   Cumming School of Medicine and Depts. of Medicine, Community Health Sciences & Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada

7. Jean‐Pierre Després

   Université Laval

   Affiliation as printed

   Department of Kinesiology, Laval University, Laval, Quebec, Canada

8. Sayem Borhan

   McMaster University

   Affiliation as printed

   Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada

9. Talha Rafiq

   McMaster University

   Affiliation as printed

   Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada

10. Romy Slebe

    Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam

    Affiliation as printed

    Department of Epidemiology and Data Science, Amsterdam University Medical Centre, Location Vrije Universiteit Amsterdam, Amsterdam, North Holland, the Netherlands

11. Denis P. Blondin

    Centre Hospitalier Universitaire de Sherbrooke

    Affiliation as printed

    Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada

12. André C. Carpentier

    Centre Hospitalier Universitaire de Sherbrooke

    Affiliation as printed

    Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada

13. Joris Hoeks

    Maastricht University

    Affiliation as printed

    Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Limburg, the Netherlands

14. Andries Kalsbeek

    Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · University of Amsterdam

    Affiliation as printed

    Department of Endocrinology and Metabolism, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, North Holland, the Netherlands

15. Patrick Schrauwen

    Maastricht University

    Affiliation as printed

    Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Limburg, the Netherlands

16. Chun‐Xia Yi

    Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · University of Amsterdam

    Affiliation as printed

    Department of Endocrinology and Metabolism, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, North Holland, the Netherlands