Skip to main content
Log in

Frequency of mutated allele CYP2D6*4 in the Turkish ankylosing spondylitis patients and healthy controls

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

The aim of this study was to determine the frequency of mutated allele CYP2D6*4 in the Turkish ankylosing spondylitis (AS) patients and healthy controls. Hundred unrelated AS patients who were diagnosed and treated in the Physical Medicine and Rehabilitation Clinic of Ankara Numune Research and Training Hospital and 52 healthy control subjects were included in the study. The wild-type allele of CYP2D6 and the mutated allele CYP2D6*4 were detected by polymerase chain reaction and a subsequent hybridization reaction. CYP2D6*4 allele was not detected in 72 subjects (72%) of the AS patients. Among the remaining 28 patients, 7 (7%) were carriers of two *4 alleles, being homozygous for CYP2D6. Twenty-one patients (21%) were carriers of one *4 allele, being heterozygous for CYP2D6*4. Among the healthy control subjects (n = 52), 23% were heterozygous and 2% were homozygous for CYP2D6*4 polymorphism. The frequency of the CYP2D6*4 allele was 0.175 in the AS patients (100 patients; 200 alleles). The frequency of the CYP2D6*4 allele was 0.134 in control group (52 control subjects; 104 alleles). The odds ratios for development of the AS for the presence of one or two CYP2D6*4 alleles with no CYP2D6*4 alleles as baseline were calculated. No significant risk of AS development was observed for individuals with one or two CYP2D6*4 alleles. Findings of this study showed no significant association between CYP2D6*4 allele and AS in our population. Further studies with larger scaled groups should be performed.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Van Der Linden S, Van Der Hiejde D, Braun J (2005) Spondyloarthopathies: ankylosing spondylitis. In: Harris (ed) Kelley’s textbook of rheumatology, vol II, 7th edn. Elsevier Saunders, Philadelphia, pp 1125–1141

  2. Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD (1973) Ankylosing spondylitis and HL-A 27. Lancet 301:904–907. doi:10.1016/S0140-6736(73)91360-3

    Article  Google Scholar 

  3. Schlosstein L, Terasaki PI, Bluestone R, Pearson CM (1973) High association of an HL-A antigen, W27, with ankylosing spondylitis. N Engl J Med 288:704–706

    PubMed  CAS  Google Scholar 

  4. Van Der Linden S, Valkenburg H, Cats A (1983) The risk of developing ankylosing spondylitis in HLA-B27 positive individuals: a family and population study. Br J Rheumatol 22(4 Suppl 2):18–19. doi:10.1093/rheumatology/22.1.18

    PubMed  Google Scholar 

  5. Braun J, Bollow M, Remlinger G, Eggens U, Rudwaleit M, Distler A, Sieper J (1998) Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum 41:58–67. doi:10.1002/1529-0131(199801)41:1<58::AID-ART8>3.0.CO;2-G

    Article  PubMed  CAS  Google Scholar 

  6. Brown MA, Kennedy LG, Darke C, Gibson K, Pile KD et al (1998) The effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis. Arthritis Rheum 41:460–465. doi:10.1002/1529-0131(199803)41:3<460::AID-ART12>3.0.CO;2-X

    Article  PubMed  CAS  Google Scholar 

  7. McGarry F, Neilly J, Anderson N, Sturrock R, Field M (2001) A polymorphism within the interleukin 1 receptor antagonist (IL-1Ra) gene is associated with ankylosing spondylitis. Rheumatology 40:1359–1364. doi:10.1093/rheumatology/40.12.1359

    Article  PubMed  CAS  Google Scholar 

  8. Timms AE, Crane AM, Sims AM et al (2004) The interleukin 1 gene cluster contains a major susceptibility locus for ankylosing spondylitis. Am J Hum Genet 75:587–595. doi:10.1086/424695

    Article  PubMed  CAS  Google Scholar 

  9. Brown MA, Edwards S, Hoyle E, Campbell S, Laval S, Daly AN et al (2000) Polymorphisms of the CYP2D6 gene increase susceptibility to ankylosing spondylitis. Hum Mol Genet 9:1563–1566. doi:10.1093/hmg/9.11.1563

    Article  PubMed  CAS  Google Scholar 

  10. Beyeler C, Armstrong M, Bird HA, Idle JR, Daly AK (1996) Relationship between genotype for the cytochrome P450 CYP2D6 and susceptibility to ankylosing spondylitis and rheumatoid arthritis. Ann Rheum Dis 55:66–68. doi:10.1136/ard.55.1.66

    Article  PubMed  CAS  Google Scholar 

  11. Carter KW, Pluzhnikov A, Timms AE, Miceli-Richard C, Bourgain C et al (2007) Combined analysis of three whole genome linkage scans for ankylosing spondylitis. Rheumatology 46:763–771. doi:10.1093/rheumatology/kel443

    Article  PubMed  CAS  Google Scholar 

  12. Sachse C, Brockmoller J, Bauer S, Roots I (1997) Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 60:284–285

    PubMed  CAS  Google Scholar 

  13. Wang SL, Huang JD, Lai MD, Lui BH, Lai ML (1993) Molecular basis of genetic variation in debrisoquine hydroxylation in Chinese subjects: polymorphism in RFLP and DNA sequence of CYP2D6. Clin Pharmacol Ther 53:410–418

    PubMed  CAS  Google Scholar 

  14. Bernard S, Neville KA, Nguyen AT, Lock-hart DA (2006) Interethnic differences in genetic polymorphisms of CYP2D6 in the US population: clinical implications. Oncologist 11:126–135. doi:10.1634/theoncologist.11-2-126

    Article  PubMed  CAS  Google Scholar 

  15. Alvan G, Bechtel P, Iselius L, Gundert-Remy U (1990) Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations. Eur J Clin Pharmacol 39:533–537. doi:10.1007/BF00316090

    Article  PubMed  CAS  Google Scholar 

  16. Johansson I, Ocarson M, Yue QY, Bertilsson L, Sjoqvist F, Ingelman-Sundberg M (1994) Genetic analysis of the Chinese cytochrome P450 2D locus: characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation. Mol Pharmacol 46:452–459

    PubMed  CAS  Google Scholar 

  17. Zanger UM, Raimundo S, Eichelbaum M (2004) Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch Pharmacol 369:23–37. doi:10.1007/s00210-003-0832-2

    Article  PubMed  CAS  Google Scholar 

  18. Koseler A, Ilcol YO, Ulus IH (2007) Frequency of mutated allele CYP2D6*4 in the Turkish population. Pharmacology 79:203–206. doi:10.1159/000100959

    Article  PubMed  CAS  Google Scholar 

  19. Aynacioglu AS, Sachse C, Bozkurt A, Kortunay S, Nacak M, Shroder T et al (1999) Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population. Clin Pharmacol Ther 66:185–192

    PubMed  CAS  Google Scholar 

  20. Aydin M, Hatirnaz O, Erensoy N, Ozbek U (2005) CYP2D6 and CYP1A1 mutations in the Turkish population. Cell Biochem Funct 23:133–135. doi:10.1002/cbf.1222

    Article  PubMed  CAS  Google Scholar 

  21. Bozkurt A, Basci NE, Isimer A, Sayal A, Kayaalp SO (1994) Polymorphic debrisoquine metabolism in a Turkish population. Clin Pharmacol Ther 55:399–401

    PubMed  CAS  Google Scholar 

  22. Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27:361–368. doi:10.1002/art.1780270401

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gonul Erden.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Erden, G., Acar, F.S., Inal, E.E. et al. Frequency of mutated allele CYP2D6*4 in the Turkish ankylosing spondylitis patients and healthy controls. Rheumatol Int 29, 1431–1434 (2009). https://doi.org/10.1007/s00296-009-0874-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-009-0874-y

Keywords

Navigation