4.6 Article

Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults

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PLOS ONE
卷 17, 期 4, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0266590

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资金

  1. Clementine Brigitta Maria Dalderup fund, Amsterdam University fund [20713, 7303]
  2. Netherlands Organization for Health Research and Development (ZonMw), The Hague [6130.0031]
  3. NZO (Dutch Dairy Association), Zoetermeer
  4. Orthica, Almere
  5. Netherlands Consortium Healthy Ageing (NCHA) Leiden/Rotterdam
  6. Ministry of Economic Affairs, Agriculture and Innovation, The Hague [KB-15-004003]
  7. Wageningen University, Wageningen
  8. VUmc, Amsterdam
  9. Erasmus Medical Center, Rotterdam
  10. Netherlands Ministry of Health, Welfare and Sports, Directorate of Long-Term Care
  11. Netherlands Organization for Scientific Research (NWO) [480-10-014]
  12. Erasmus MC University Medical Center Rotterdam
  13. Erasmus University Rotterdam
  14. Netherlands Organisation for Scientific Research (NWO)
  15. The Netherlands Organisation for Health Research and Development (ZonMw)
  16. Research Institute for Diseases in the Elderly (RIDE)
  17. Netherlands Genomics Initiative (NGI)
  18. Ministry of Education, Culture and Science
  19. Ministry of Health, Welfare and Sports
  20. European Commission (DG XII)
  21. Municipality of Rotterdam
  22. Welsh Government
  23. British Heart Foundation
  24. Cancer Research UK
  25. Diabetes UK
  26. National Health Service (NHS)
  27. Wellcome Trust
  28. MRC
  29. NIHR
  30. Department of Health
  31. Medical Research Council

向作者/读者索取更多资源

This study reveals that certain genetic variants may modify the fall risk associated with antidepressant use, but inconsistent results across studies highlight the need for validation in a prospective-designed study. Pharmacogenetics could potentially have value in preventing falls through antidepressant (de)prescribing.
Background Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users. Methods The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated. Results In antidepressant users(n = 566), for rs28371725 (CYP2D6* 41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26-0.80). Concerning rs1057910 (CYP2C9* 3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17-3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07-2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05-3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D* 41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01-1.12). G/non-variant-allele of rs4244285 (CY2C19* 2) was associated with decreased risk (OR = 0.96, 95% CI 0.92-1.00). Conclusion This is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention.

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