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Lack of Association Between Endometriosis and N-acetyl transferase 1 (NAT1) and 2 (NAT2) Polymorphisms in a Japanese Population

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Abstract

Objective

We investigated the association between endometriosis and polymorphisms in the N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT 2) genes in a Japanese population, having previously demonstrated a positive association with NAT2 polymorphisms in a UK population.

Methods

Genotyping for NAT1 alleles *3, *4, *10, and *11, and NAT2 alleles *4, *5A, *5B, *5C, *6A, and *7B was performed using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and allele-specific PCR (AS-PCR) analysis in 145 ethnically Japanese, endometriosis patients and 182 controls. The NAT1 and NAT2 allele and genotype frequencies were compared in cases and controls using the Fisher exact test.

Results

No significant differences between cases and controls were observed in the frequencies of the NAT1 and NAT2 alleles (P =. 13; P =.91) and genotypes (P =.24; P =.79), and the NAT2 acetylation phenotypes (P =.46). Dividing the cases into a subgroup, consisting of women with severe disease only (n = 80), had no effect on the results.

Conclusion

The distribution of NAT1 and NAT2 allele and genotype frequencies were not significantly different between Japanese cases and controls. Our findings suggest that polymorphisms in NAT1 and NAT2 are unlikely to be associated with an increased risk of endometriosis in the Japanese population.

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References

  1. Kennedy SH, Mardon H, Barlow D. Familial endometriosis. J Assist Reprod Genet 1995;12:32–4.

    Article  CAS  PubMed  Google Scholar 

  2. Stefansson H, Geirsson RT, Steinthorsdottir V, et al. Genetic factors contribute to the risk of developing endometriosis. Hum Reprod 2002;17:555–9.

    Article  CAS  PubMed  Google Scholar 

  3. Hadfield RM, Mardon HJ, Barlow DH, Kennedy SH. Endometriosis in monozygotic twins. Fertil Steril 1997;68:941–2.

    Article  CAS  PubMed  Google Scholar 

  4. Treloar SA, O’Connor DT, VM, Martin NG. Genetic influences on endometriosis in an Australian twin sample. Fertil Steril 1999;71:701–10.

    Article  CAS  PubMed  Google Scholar 

  5. Moen MH. Endometriosis in monozygotic twins. Acta Obstet Gynecol Scand 1994;73:59–62.

    Article  CAS  PubMed  Google Scholar 

  6. Coxhead D, Thomas EJ. Familial inheritance of endometriosis in a British population. A case control study. J Obstet Gynaecol 1993;13:42–4.

    Article  Google Scholar 

  7. Moen MH, Magnus P. The familial risk of endometriosis. Acta Obstet Gynecol Scand 1993;72:560–4.

    Article  CAS  PubMed  Google Scholar 

  8. Simpson JL, Elias S, Malinak LR, Buttram VC Jr. Heritable aspects of endometriosis. I. Genetic studies. Am J Obstet Gynecol 1980;137:327–31.

    Article  CAS  PubMed  Google Scholar 

  9. Zondervan KT, Cardon LR, Kennedy SH. The genetic basis of endometriosis. Curr Opin Obstet Gynecol 2001;13:309–14.

    Article  CAS  PubMed  Google Scholar 

  10. Rier SE, Martin DC, Bowman RE, Dmowski WP, Becker JL. Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fundam Appl Toxicol 1993;21:433–41.

    Article  CAS  PubMed  Google Scholar 

  11. Mayani A, Barel S, Soback S, Almagor M. Dioxin concentrations in women with endometriosis. Hum Reprod 1997;12:373–5.

    Article  CAS  PubMed  Google Scholar 

  12. Koninckx PR, Braet P, Kennedy SH, Barlow DH. Dioxin pollution and endometriosis in Belgium. Hum Reprod 1994;9:1001–2.

    Article  CAS  PubMed  Google Scholar 

  13. Lebel G, Dodin S, Ayotte P, Marcoux S, Ferron LA, Dewailly E. Organochlorine exposure and the risk of endometriosis. Fertil Steril 1998;69:221–8.

    Article  CAS  PubMed  Google Scholar 

  14. Matas N, Thygesen P, Stacey M, Risch A, Sim E. Mapping AAC1, AAC2 and AACP, the genes for arylamine N-acetyltrans-ferases, carcinogen metabolising enzymes on human chromosome 8p22, a region frequently deleted in tumours. Cytogenet CeU Genet 1997;77:290–5.

    Article  CAS  Google Scholar 

  15. Blum M, Grant DM, McBride W, Heim M, Meyer UA. Human arylamine N-acetyltransferase genes: Isolation, chromosomal localization, and functional expression. DNA Cell Biol 1990;9:193–203.

    Article  CAS  PubMed  Google Scholar 

  16. Hein DW, Doll MA, Fretland AJ, et al. Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Cancer Epidemiol Biomarkers Prev 2000;9:29–42.

    CAS  PubMed  Google Scholar 

  17. Minchin RF, Reeves PT, Teitel CH, et al. N- and O-acetylation of aromatic and heterocyclic amine carcinogens by human monomorphic and polymorphic acetyltransferases expressed in COS-1 cells. Biochem Biophys Res Commun 1992;185:839–44.

    Article  CAS  PubMed  Google Scholar 

  18. Cartwright RA, Glashan RW, Rogers HI, et al. Role of N-acetyltransferase phenotypes in bladder carcinogenesis: A pharmacogenetic epidemiological approach to bladder cancer. Lancet 1982;2:842–5.

    Article  CAS  PubMed  Google Scholar 

  19. Gago-Dominguez M, Bell DA, Watson MA, et al. Permanent hair dyes and bladder cancer: risk modification by cytochrome P4501A2 and N-acetyltransferases 1 and 2. Carcinogenesis 2003;24:483–9.

    Article  CAS  PubMed  Google Scholar 

  20. Inatomi H, Katoh T, Kawamoto T, Matsumoto T. NAT2 gene polymorphism as a possible marker for susceptibility to bladder cancer in Japanese. Int J Urol 1999;6:446–54.

    Article  CAS  PubMed  Google Scholar 

  21. Ilett KF, David BM, Detchon P, Castleden WM, Kwa R. Acetylation phenotype in colorectal carcinoma. Cancer Res 1987;47:1466–9.

    CAS  PubMed  Google Scholar 

  22. Gil JP, Lechner MC. Increased frequency of wild-type arylamine-N-acetyltransferase allele NAT2*4 homozygotes in Portuguese patients with colorectal cancer. Carcinogenesis 1998;19:37–41.

    Article  CAS  PubMed  Google Scholar 

  23. Roberts-Thomson IC, Ryan P, Khoo KK, Hart WJ, McMichael AJ, Butler RN. Diet, acetylator phenotype, and risk of colorectal neoplasia. Lancet 1996;347:1372–4.

    Article  CAS  PubMed  Google Scholar 

  24. Cascorbi I, Brockmoller J, Mrozikiewicz PM, Bauer S, Loddenkemper R, Roots I. Homozygous rapid arylamine N-acetyltrans-ferase (NAT2) genotype as a susceptibility factor for lung cancer. Cancer Res 1996;56:3961–6.

    CAS  PubMed  Google Scholar 

  25. Nyberg F, Hou SM, Hemminki K, Lambert B, Pershagen G. Glutathione S-transferase Ml and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls. Cancer Epidemiol Biomarkers Prev 1998;7:875–83.

    CAS  PubMed  Google Scholar 

  26. Varzim G, Monteiro E, Silva R, Pinheiro C, Lopes C. Polymorphisms of arylamine N-acetyltransferase (NAT1 and NAT2) and larynx cancer susceptibility. ORL J Otorhinolaryngol Relat Spec 2002;64:206–12.

    Article  CAS  PubMed  Google Scholar 

  27. Sardas S, Cok I, Sardas OS, Ilhan O, Karakaya AE. Polymorphic N-acetylation capacity in breast cancer patients. Int J Cancer 1990;46:1138–9.

    Article  CAS  PubMed  Google Scholar 

  28. Millikan RC, Pittman GS, Newman B, et al. Cigarette smoking, N-acetyltransferases 1 and 2, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 1998;7:371–8.

    CAS  PubMed  Google Scholar 

  29. Ambrosone CB, Freudenheim JL, Graham S, et al. Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk. JAMA 1996;276:1494–1501.

    Article  CAS  PubMed  Google Scholar 

  30. Huang CS, Chern HD, Shen CY, Chang KJ. Association between N-acetyltransferase 2 (NAT2) genetic polymorphism and development of breast cancer in post-menopausal Chinese women in Taiwan, an area of great increase in breast cancer incidence. Int J Cancer 1999;82:175–9.

    Article  CAS  PubMed  Google Scholar 

  31. Hsieh FI, Pu YS, Chern HD, Hsu LI, Chiou HY, Chen CJ. Genetic polymorphisms of N-acetyltransferase 1 and 2 and risk of cigarette smoking-related bladder cancer. Br J Cancer 1999;81:537–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Fukutome K, Watanabe M, Shiraishi T, et al. N-acetyltransferase 1 genetic polymorphism influences the risk of prostate cancer development. Cancer Lett 1999;136:83–7.

    Article  CAS  PubMed  Google Scholar 

  33. Hein DW, Leff MA, Ishibe N, et al. Association of prostate cancer with rapid N-acetyltransferase 1 (NAT1*10) in combination with slow N-acetyltransferase 2 acetylator genotypes in a pilot case-control study. Environ Mol Mutagen 2002;40:161–7.

    Article  CAS  PubMed  Google Scholar 

  34. Wikman H, Thiel S, Jager B, et al. Relevance of N-acetyltransferase 1 and 2 (NAT1, NAT2) genetic polymorphisms in non-small cell lung cancer susceptibility. Pharmacogenetics 2001;11:157–68.

    Article  CAS  PubMed  Google Scholar 

  35. Boissy RJ, Watson MA, Umbach DM, et al. A pilot study investigating the role of NAT1 and NAT2 polymorphisms in gastric adenocarcinoma. Int J Cancer 2000;87:507–11.

    Article  CAS  PubMed  Google Scholar 

  36. Baranova H, Canis M, Ivaschenko T, et al. Possible involvement of arylamine N-acetyltransferase 2, glutathione S- transferases M1 and T1 genes in the development of endometriosis. Mol Hum Reprod 1999;5:636–41.

    Article  CAS  PubMed  Google Scholar 

  37. Nakago S, Hadfield RM, Zondervan KT, et al. Association between endometriosis and N-acetyltransferase 2 polymorphisms in a UK population. Mol Hum Reprod 2001;7:1079–83.

    Article  CAS  PubMed  Google Scholar 

  38. The American Fertility Society. Revised American Fertility Society classification of endometriosis: 1985. Fertil Steril 1985;43:351–2.

    Article  Google Scholar 

  39. Zondervan KT, Cardon LR, Kennedy SH. What makes a good case-control study? Design issues for complex traits such as endometriosis. Hum Reprod 2002;17:1415–23.

    Article  PubMed  Google Scholar 

  40. Koninckx PR, Oosterlynck D, D’Hooghe T, Meuleman C. Deeply infiltrating endometriosis is a disease whereas mild endometriosis could be considered a non-disease. Ann N Y Acad Sci 1994;734:333–41.

    Article  CAS  PubMed  Google Scholar 

  41. Payton MA, Sim E. Genotyping human arylamine N-acetyltransferase type 1 (NAT1): The identification of two novel allelic variants. Biochem Pharmacol 1998;55:361–6.

    Article  CAS  PubMed  Google Scholar 

  42. Katoh T, Kaneko S, Boissy R, Watson M, Ikemura K, Bell DA. A pilot study testing the association between N-acetyltransferases 1 and 2 and risk of oral squamous cell carcinoma in Japanese people. Carcinogenesis 1998;19:1803–7.

    Article  CAS  PubMed  Google Scholar 

  43. Okumura K, Kita T, Chikazawa S, Komada F, Iwakawa S, Tanigawara Y. Genotyping of N-acetylation polymorphism and correlation with procainamide metabolism. Clin Pharmacol Ther 1997;61:509–17.

    Article  CAS  PubMed  Google Scholar 

  44. Hickman D, Sim E. N-acetyltransferase polymorphism. Comparison of phenotype and genotype in humans. Biochem Pharmacol 1991;42:1007–14.

    CAS  PubMed  Google Scholar 

  45. Hickman D, Risch A, Camilleri JP, Sim E. Genotyping human polymorphic arylamine N-acetyltransferase: Identification of new slow allotypic variants. Pharmacogenetics 1992;2:217–26.

    Article  CAS  PubMed  Google Scholar 

  46. Vatsis KP, Weber WW, Bell DA, et al. Nomenclature for N-acetyltransferases. Pharmacogenetics 1995;5:1–17.

    Article  CAS  PubMed  Google Scholar 

  47. Butcher NJ, Boukouvala S, Sim E, Minchin RF. Pharmacogenetics of the arylamine N-acetyltransferases. Pharmacogenomics J 2002;2:30–42.

    Article  CAS  PubMed  Google Scholar 

  48. Gonzalez MV, Alvarez V, Pello MF, Menendez MJ, Suarez C, Coto E. Genetic polymorphism of N-acetyltransferase-2, glutathione S-transferase-M1, and cytochromes P450IIE1 and P450IID6 in the susceptibility to head and neck cancer. J Clin Pathol 1998;51:294–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cooper GS, Treadwell EL, Dooley MA, St Clair EW, Gilkeson GS, Taylor JA. N-acetyl transferase genotypes in relation to risk of developing systemic lupus erythematosus. J Rheumatol 2004;31:76–80.

    CAS  PubMed  Google Scholar 

  50. Korpinen E, Groop PH, Rautio A, et al. N-acetyltransferase-2 polymorphism, smoking and type 1 diabetic nephropathy. Pharmacogenetics 1999;9:627–33.

    Article  CAS  PubMed  Google Scholar 

  51. Bandmann O, Vaughan JR, Holmans P, Marsden CD, Wood NW. Detailed genotyping demonstrates association between the slow acetylator genotype for N-acetyltransferase 2 (NAT2) and familial Parkinson’s disease. Mov Disord 2000;15:30–5.

    Article  CAS  PubMed  Google Scholar 

  52. Ogawa M. Biochemical, molecular genetic and ecogenetic studies of polymorphic arylamine N-acetyltransferase (NAT2) in the brain. Fukuoka Igaku Zasshi 1999;90:118–31.

    CAS  PubMed  Google Scholar 

  53. Le Marchand L, Hankin JH, Wilkens LR, et al. Combined effects of well-done red meat, smoking, and rapid N-acetyltransferase 2 and CYP1A2 phenotypes in increasing colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2001;10:1259–66.

    PubMed  Google Scholar 

  54. Butcher NJ, Ilett KF, Minchin RF. Substrate-dependent regulation of human arylamine N-acetyltransferase-1 in cultured cells. Mol Pharmacol 2000;57:468–73.

    Article  CAS  PubMed  Google Scholar 

  55. Green J, Banks E, Berrington A, Darby S, Deo H, Newton R. N-acetyltransferase 2 and bladder cancer: An overview and consideration of the evidence for gene-environment interaction. Br J Cancer 2000;83:412–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hadfield R, Mardon H, Barlow D, Kennedy S. Delay in the diagnosis of endometriosis: A survey of women from the USA and the UK. Hum Reprod 1996;11:878–80.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Takeshi Maruo MD, PhD.

Additional information

Supported by a Grant-in-Aid for Scientific Research 16024212 from the Japanese Ministry of Education, Science and Culture and the Japan Association of Obstetricians and Gynecologists Ogyaa-Donation Foundation (JODF).

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Deguchi, M., Yoshida, S., Kennedy, S. et al. Lack of Association Between Endometriosis and N-acetyl transferase 1 (NAT1) and 2 (NAT2) Polymorphisms in a Japanese Population. Reprod. Sci. 12, 208–213 (2005). https://doi.org/10.1016/j.jsgi.2005.01.008

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