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Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts
  1. B L Browning1,2,3,
  2. V Annese18,
  3. M L Barclay4,5,
  4. S A Bingham6,
  5. S Brand7,
  6. C Büning8,
  7. M Castro9,
  8. S Cucchiara10,
  9. B Dallapiccola11,
  10. H Drummond12,
  11. L R Ferguson1,3,
  12. A Ferraris11,
  13. S A Fisher13,
  14. R B Gearry4,5,
  15. J Glas7,14,
  16. L Henckaerts15,
  17. C Huebner1,3,
  18. D Knafelz9,
  19. L Lakatos16,
  20. P L Lakatos17,
  21. A Latiano18,
  22. X Liu19,20,21,22,
  23. C Mathew13,
  24. B Müller-Myhsok23,
  25. W G Newman24,
  26. E R Nimmo12,
  27. C L Noble12,
  28. O Palmieri18,
  29. M Parkes25,
  30. I Petermann1,3,
  31. P Rutgeerts15,
  32. J Satsangi12,
  33. A N Shelling3,26,
  34. K A Siminovitch19,20,21,22,
  35. H-P Török7,27,
  36. M Tremelling25,
  37. S Vermeire15,
  38. M R Valvano18,
  39. H Witt28,29
  1. 1
    Discipline of Nutrition, University of Auckland, Auckland, New Zealand
  2. 2
    Department of Statistics, University of Auckland, Auckland, New Zealand
  3. 3
    Nutrigenomics, New Zealand
  4. 4
    Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
  5. 5
    Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand
  6. 6
    EPIC Norfolk and MRC Centre for Nutrition and Cancer Prevention and Survival, University of Cambridge, Cambridge, UK
  7. 7
    Department of Medicine II– Grosshadern, University of Munich, Munich, Germany
  8. 8
    Department of Gastroenterology, Hepatology and Endocrinology, Charité, Campus Mitte, Universitätsmedizin Berlin, Berlin, Germany
  9. 9
    Gastroenterology Unit, IRCCS, Bambino Gesù Children’s Hospital, Rome, Italy
  10. 10
    Department of Pediatrics, University of Rome La Sapienza, Rome, Italy
  11. 11
    IRCCS CSS-Mendel Institute, Rome, Italy
  12. 12
    Gastrointestinal Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK
  13. 13
    Department of Medical and Molecular Genetics, King’s College London School of Medicine, London, UK
  14. 14
    Department of Restorative Dentistry and Periodontology, University of Munich, Munich, Germany
  15. 15
    Department of Gastroenterology, UZ Gasthuisberg, Leuven, Belgium
  16. 16
    First Department of Medicine, Csolnoky F. County Hospital, Veszprem, Hungary
  17. 17
    First Department of Medicine, Semmelweis University, Budapest, Hungary
  18. 18
    Department of Gastroenterology, IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
  19. 19
    Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  20. 20
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada
  21. 21
    Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario, Canada
  22. 22
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
  23. 23
    Max-Planck Institute of Psychiatry, Munich, Germany
  24. 24
    Department of Medical Genetics, University of Manchester, Manchester, UK
  25. 25
    Department of Gastroenterology, Addenbrookes Hospital, Cambridge, UK
  26. 26
    Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand
  27. 27
    Department of Surgery– Innenstadt, University of Munich, Munich, Germany
  28. 28
    Department of Pediatrics, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany
  29. 29
    Department of Gastroenterology and Hepatology, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany
  1. B L Browning, Discipline of Nutrition, The University of Auckland, Private Bag 92019, Auckland, New Zealand; b.browning{at}auckland.ac.nz

Abstract

Background: DLG5 p.R30Q has been reported to be associated with Crohn disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case–control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male–female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD.

Methods: DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male–female frequency differences in controls and for case–control frequency differences in men and in women.

Results: The data showed no male–female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR = 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR = 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p = 0.010, OR = 0.86, 95% CI 0.76 to 0.97), but not in men.

Conclusion: DLG5 30Q is associated with a small reduction in risk of CD in women.

https://doi.org/10.1136/jmg.2007.050773

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    Footnotes

    • Competing interests: None declared.