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Association of angiotensin-converting enzyme (ACE) gene insertion–deletion polymorphism with spondylarthropathies

  • Published:
Journal of Biomedical Science

Summary

Low back pain (LBP) is a common medical problem. Interaction between genetic and environmental factors predisposes individuals to LBP even at an early age. Inflammatory back pain or spondylarthropathies include ankylosing spondylitis (AS), psoriatic arthritis (PSA), reactive arthritis enteropathic and undifferentiated arthropathies. Angiotensin-converting enzyme (ACE) plays an important role in circulatory homeostasis, physiology of vasculature and inflammation. The insertion–deletion (I/D) polymorphism of the ACE gene has been shown to determine the plasma and tissue levels of ACE especially in the synovial fluid. The aim of this study was to investigate an association between ACE gene I/D polymorphism and inflammatory back pain (spondylarthropathies) secondary to ankylosing spondylitis (AS), psoriatic arthritis, inflammatory bowel disease and undifferentiated spondylarthropathies. The prevalence of ACE gene I/D polymorphism genotypes was determined in 63 patients with inflammatory back pain by polymerase chain reaction (PCR) and compared with that in 111 healthy controls. Of the 63 patients studied, 45 (71.4%) were with AS, 13 (20.6%) were with PSA, 4 (6.3%) were with reactive arthropathy and 1 (1.6%) manifested undifferentiated arthropathy. There were 43 males and 20 females. Mean age of patients was 39.0 ± 11.36 years, age at onset of spondylarthropathy was 27.7 ± 7.49 years and disease duration was 10.3 ± 7.74 months. The controls were selected to match with the patients group in terms of gender ratio, age and ethnicity. The ACE gene polymorphism showed an overall significant difference between patients and controls (p = 0.050). When the ID and II genotype frequency was combined and compared with that for DD genotype amongst patient and control groups, a considerably higher incidence was detected for ID and II genotypes than the DD genotype in spondylarthropathy patients compared to that in the controls (p = 0.036). This study showed a significant association of the I-allele of ACE gene I/D polymorphism with spondylarthropathy in Kuwaiti Arabs.

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References

  1. Hart L.G., Deo R.A., Cherkin D.C. (1995) Physicians office visits for low back pain: frequency, clinical evaluation and treatment patterns from a US national survey. Spine; 20:11–19

    Article  PubMed  CAS  Google Scholar 

  2. Skovron M.L. (1992) Epidemiology of low back pain. Baillieres Clin. Rheumatol. 6:559–573

    Article  PubMed  CAS  Google Scholar 

  3. Leboeuf-Y de C., Klougart N., Lauritzen T. (1996) How common is low back pain in Nordic population? Spine 21:1518–1525

    Article  Google Scholar 

  4. Al-Awadhi A., Olusi S., Moussa M., Shehab D., Al-Zaid N., Al-Herz A., Al-Jarallah K. (2004) Musculoskeletal pain, disability and health-seeking behavior in adult Kuwaitis using a validated Arabic version of the WHO-ILAR COPCORD core questionnaire. Clin. Exp. Rheumatol. 22:177–183

    PubMed  CAS  Google Scholar 

  5. Shehab D., Al-Jarallah K., Moussa M.A.A., Adham N. (2003) Prevalence of low back pain among physical therapists in Kuwait. Med. Princ. Pract. 12:224–230

    Article  PubMed  Google Scholar 

  6. Shehab D., Al-Jarallah K., Al-Ghareeb F., Sanaseeri S., Al-Fadhli M., Habeeb S. (2004) Is low back pain prevalent among Kuwaiti children and adolescents? Med. Princ. Pract. 13:142–146

    Article  PubMed  Google Scholar 

  7. Shehab D., Al-Jarallah K. (2005) Non-specific low back pain in Kuwaiti children and adolescents: associated factors. J. Adolesc. Health 36:32–35

    Article  PubMed  Google Scholar 

  8. Lee Y.H., Hee Y., Seong J., Jong D., Gwan G. (2006) Angiotensin-converting enzyme insertion/deletion polymorphism and systemic lupus erythematosis. J. Rheumatol. 33:698–702

    PubMed  CAS  Google Scholar 

  9. Turgut S., Turgut G., Atalay E., Atalay A. (2005) Angiotensin-converting enzyme. I/D polymorphism in Behcet’s disease. Med. Princ. Pract. 14:213–216

    Article  PubMed  Google Scholar 

  10. Ozkur M., Erbagci Z., Nacak M., Tuncal A.A., Alasehirli B., Aynacioglu A.S. (2004) Association of insertion/deletion polymorphism of the angiotensin-converting enzyme gene with psoriasis. Br. J. Rheumatol. 151:792–795

    CAS  Google Scholar 

  11. Al Saeid K., Haider M., Ayoub E. (2003) Angiotensin-converting enzyme gene insertion–deletion polymorphism is associated with juvenile rheumatoid arthritis. J. Rheumatol. 30:2705–2709

    CAS  Google Scholar 

  12. Alhenc-Gelas F., Weare J.A., Johnson R.L. et al. (1983) Measurement of human converting enzyme level b y direct radioimmunoassay. J. Lab. Clin. Med. 101:83–96

    PubMed  CAS  Google Scholar 

  13. Humphries S.E. (1988) DNA polymorphisms of the apolipoprotein genes. Their use in the investigation of the genetic component of hyperlipidemia and atherosclerosis. Atherosclerosis 72:89–108

    Article  PubMed  CAS  Google Scholar 

  14. Cambien F., Alhenc-Gelas F., Herbeth B. et al. (1988) Familial resemblance of plasma angiotensin-converting enzyme level: The Nancy Study. Am. J. Hum. Genet. 43:774–780

    PubMed  CAS  Google Scholar 

  15. Soubrier F., Martin S., Alonso A. et al. (2002) High-resolution genetic mapping of the ACE-lined QTL influencing circulatory ACE activity. Eur. J. Hum. Genet. 10:553–561

    Article  PubMed  CAS  Google Scholar 

  16. Tiret L., Rigat B., Visvikis S. et al. (1992) Evidence from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am. J. Hum. Genet. 51:197–205

    PubMed  CAS  Google Scholar 

  17. McKenzie C.A., Julier C., Forrester T. et al. (1995) Segregation and linkage analysis of serum angiotensin I-converting enzyme levels: evidence for two quantitative-trait loci. Am. J. Hum. Genet. 57:1426–1435

    PubMed  CAS  Google Scholar 

  18. Villard E., Tiret L., Visvikis S. et al. (1996) Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis. Am. J. Hum. Genet. 58:1268–1278

    PubMed  CAS  Google Scholar 

  19. Hubert C., Houot A.M., Corvol P., Soubrier F. (1991) Structure of the angiotensin I-converting enzyme gene: two alternate promoters correspond to evolutionary steps of a duplicated gene. J. Biol. Chem. 266:15377–15383

    PubMed  CAS  Google Scholar 

  20. Montgomery H., Clarkson P., Barnard M. et al. (1999) Angiotensin-converting enzyme gene insertion/deletion polymorphism and response to physical training. Lancet 353:541–545

    Article  PubMed  CAS  Google Scholar 

  21. Walsh D.A., Catravas J., Wharton J. (2000) Angiotensin converting enzyme in human synovium: increased stromal [(125)I]351 A binding in rheumatoid arthritis. Ann. Rheum. Dis. 59:125–131

    Article  PubMed  CAS  Google Scholar 

  22. Dougados M., Van der Linden S., Juhlia R. et al. (1991) The European Spondyloarthropathy Study Group, preliminary criteria for the classification of spondyloarthropathy. Arthritis Rheum. 34(10):1218–1227

    Article  PubMed  CAS  Google Scholar 

  23. Teebi A.S. and Farag T.I., Population dimensions in the Arab world. In: Genetic Disorders Among Arab Populations. Oxford University Press, Oxford, UK, 1997, p. 29

  24. Sambrook J., Freitsch E.F., Maniatis T. (1989) Molecular Cloning: A Laboratory Manual, 2nd ed. Cold Spring Harbor Laboratory, NY, USA

    Google Scholar 

  25. Rigat B., Hubert C., Alhenc-Gelas F. (1990) An insertion–deletion polymorphism of angiotensin converting enzyme gene accounts for half the variance of serum enzyme levels. J. Clin. Invest. 86:1343–1346

    Article  PubMed  CAS  Google Scholar 

  26. Rudwaleit M., Metter A., Listing J., Sieper J., Braun J. (2006) Inflammatory back pain in ankylosing spondylitis. Arthritis Rheum. 54(2):569–578

    Article  PubMed  Google Scholar 

  27. Samani N.J., Thompson J.R., O’Toole L., Channer K., Woods K.L. (1996) A meta-analysis of the association of the deletion allele at the angiotensin converting enzyme gene with myocardial infarction. Circulation 94:708–712

    PubMed  CAS  Google Scholar 

  28. Webb D.J., Gonias S.L. (1998) A modified human alpha-2-macroglobulin derivative that binds tumor necrosis factor-alpha and interleukin-1 beta with high affinity in␣vitro and reverses lipopolysaccharide toxicity in␣vivo in mice. Lab. Invest. 78:939–948

    PubMed  CAS  Google Scholar 

  29. Brock J.W., Hunley T.E., Adams M.C., Kon V. (1998) Role of the rennin–angiotensin system in disorders of the urinary tract. J. Urol. 160:1812–1819

    Article  PubMed  CAS  Google Scholar 

  30. Ray P.E., Bruggeman L.A., Horikoshi S., Aguilera G., Klotman P.E. (1994) Angiotensin-II stimulates human fetal mesangial cell proliferation and fibronectin biosysnthesis by binding to AT1 receptors. Kidney Int. 45:177–185

    Article  PubMed  CAS  Google Scholar 

  31. Vaele D., Yanni G., Bresnihan B., FitzGerald O. (1992) Production of angiotensin converting enzyme by rheumatoid synovial membrane. Ann. Rheum. Dis. 51:476–480

    Google Scholar 

  32. Walsh D.A., Suzuki T., Knock G.A., Blake D.R., Polak J.M., Whjarton J. (1994) AT1 receptor characteristics of angiotensin analogue binding in human synovium. Br. J. Pharmacol. 112:435–442

    PubMed  CAS  Google Scholar 

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Acknowledgments

This study was funded by a grant from Kuwait University Research Administration (Project No. RM 01/05). The technical assistance of Mrs. Jalaja Sukumaran and Mr. Irfan Ahmad is thankfully acknowledged. We would like to thank Dr␣P.N. Sharma for his help in statistical analysis.

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Correspondence to Mohammad Z. Haider.

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Shehab, D.K., Al-Jarallah, K.F., Al-Awadhi, A.M. et al. Association of angiotensin-converting enzyme (ACE) gene insertion–deletion polymorphism with spondylarthropathies. J Biomed Sci 15, 61–67 (2008). https://doi.org/10.1007/s11373-007-9203-1

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  • DOI: https://doi.org/10.1007/s11373-007-9203-1

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