A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients

M. Tohkin; N. Kaniwa; Y. Saito; E. Sugiyama; K. Kurose; J. Nishikawa; R. Hasegawa; M. Aihara; K. Matsunaga; M. Abe; H. Furuya; Y. Takahashi; H. Ikeda; M. Muramatsu; M. Ueta; C. Sotozono; S. Kinoshita; Z. Ikezawa

doi:10.1038/tpj.2011.41

A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients

M. Tohkin, N. Kaniwa, Y. Saito, E. Sugiyama, K. Kurose, J. Nishikawa, R. Hasegawa, M. Aihara, K. Matsunaga, M. Abe, H. Furuya, Y. Takahashi, H. Ikeda, M. Muramatsu, M. Ueta, C. Sotozono, S. Kinoshita, Z. Ikezawa

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Abstract

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe, cutaneous adverse drug reactions that are rare but life threatening. Genetic biomarkers for allopurinol-related SJS/TEN in Japanese were examined in a genome-wide association study in which Japanese patients (n=14) were compared with ethnically matched healthy controls (n=991). Associations between 890 321 single nucleotide polymorphisms and allopurinol-related SJS/TEN were analyzed by the Fisher's exact test (dominant genotype mode). A total of 21 polymorphisms on chromosome 6 were significantly associated with allopurinol-related SJS/TEN. The strongest association was found at rs2734583 in BAT1, rs3094011 in HCP5 and GA005234 in MICC (P=2.44 × 10-8; odds ratio=66.8; 95% confidence interval, 19.8-225.0). rs9263726 in PSORS1C1, also significantly associated with allopurinol-related SJS/TEN, is in absolute linkage disequilibrium with human leukocyte antigen-B*5801, which is in strong association with allopurinol-induced SJS/TEN. The ease of typing rs9263726 makes it a useful biomarker for allopurinol-related SJS/TEN in Japanese.

Original language	English
Pages (from-to)	60-69
Number of pages	10
Journal	Pharmacogenomics Journal
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/tpj.2011.41
Publication status	Published - 02-2013

All Science Journal Classification (ASJC) codes

Molecular Medicine
Genetics
Pharmacology

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10.1038/tpj.2011.41

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Tohkin, M., Kaniwa, N., Saito, Y., Sugiyama, E., Kurose, K., Nishikawa, J., Hasegawa, R., Aihara, M., Matsunaga, K., Abe, M., Furuya, H., Takahashi, Y., Ikeda, H., Muramatsu, M., Ueta, M., Sotozono, C., Kinoshita, S., & Ikezawa, Z. (2013). A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients. Pharmacogenomics Journal, 13(1), 60-69. https://doi.org/10.1038/tpj.2011.41

@article{424ee783c2ed4306b6c8bf7ecea604d5,

title = "A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients",

abstract = "Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe, cutaneous adverse drug reactions that are rare but life threatening. Genetic biomarkers for allopurinol-related SJS/TEN in Japanese were examined in a genome-wide association study in which Japanese patients (n=14) were compared with ethnically matched healthy controls (n=991). Associations between 890 321 single nucleotide polymorphisms and allopurinol-related SJS/TEN were analyzed by the Fisher's exact test (dominant genotype mode). A total of 21 polymorphisms on chromosome 6 were significantly associated with allopurinol-related SJS/TEN. The strongest association was found at rs2734583 in BAT1, rs3094011 in HCP5 and GA005234 in MICC (P=2.44 × 10-8; odds ratio=66.8; 95% confidence interval, 19.8-225.0). rs9263726 in PSORS1C1, also significantly associated with allopurinol-related SJS/TEN, is in absolute linkage disequilibrium with human leukocyte antigen-B*5801, which is in strong association with allopurinol-induced SJS/TEN. The ease of typing rs9263726 makes it a useful biomarker for allopurinol-related SJS/TEN in Japanese.",

author = "M. Tohkin and N. Kaniwa and Y. Saito and E. Sugiyama and K. Kurose and J. Nishikawa and R. Hasegawa and M. Aihara and K. Matsunaga and M. Abe and H. Furuya and Y. Takahashi and H. Ikeda and M. Muramatsu and M. Ueta and C. Sotozono and S. Kinoshita and Z. Ikezawa",

note = "Funding Information: We thank all the patients and physicians for their cooperation with this study. We also thank Riken Genesis for the Illumina BeadChip analysis and StaGen for the statistical analysis. This study was supported in part by a Health and Labor Science Research Grant (Research on Advanced Medical Technology) from the Ministry of Health, Labor and Welfare of Japan.",

year = "2013",

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doi = "10.1038/tpj.2011.41",

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Tohkin, M, Kaniwa, N, Saito, Y, Sugiyama, E, Kurose, K, Nishikawa, J, Hasegawa, R, Aihara, M, Matsunaga, K, Abe, M, Furuya, H, Takahashi, Y, Ikeda, H, Muramatsu, M, Ueta, M, Sotozono, C, Kinoshita, S & Ikezawa, Z 2013, 'A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients', Pharmacogenomics Journal, vol. 13, no. 1, pp. 60-69. https://doi.org/10.1038/tpj.2011.41

TY - JOUR

T1 - A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients

AU - Tohkin, M.

AU - Kaniwa, N.

AU - Saito, Y.

AU - Sugiyama, E.

AU - Kurose, K.

AU - Nishikawa, J.

AU - Hasegawa, R.

AU - Aihara, M.

AU - Matsunaga, K.

AU - Abe, M.

AU - Furuya, H.

AU - Takahashi, Y.

AU - Ikeda, H.

AU - Muramatsu, M.

AU - Ueta, M.

AU - Sotozono, C.

AU - Kinoshita, S.

AU - Ikezawa, Z.

N1 - Funding Information: We thank all the patients and physicians for their cooperation with this study. We also thank Riken Genesis for the Illumina BeadChip analysis and StaGen for the statistical analysis. This study was supported in part by a Health and Labor Science Research Grant (Research on Advanced Medical Technology) from the Ministry of Health, Labor and Welfare of Japan.

PY - 2013/2

Y1 - 2013/2

N2 - Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe, cutaneous adverse drug reactions that are rare but life threatening. Genetic biomarkers for allopurinol-related SJS/TEN in Japanese were examined in a genome-wide association study in which Japanese patients (n=14) were compared with ethnically matched healthy controls (n=991). Associations between 890 321 single nucleotide polymorphisms and allopurinol-related SJS/TEN were analyzed by the Fisher's exact test (dominant genotype mode). A total of 21 polymorphisms on chromosome 6 were significantly associated with allopurinol-related SJS/TEN. The strongest association was found at rs2734583 in BAT1, rs3094011 in HCP5 and GA005234 in MICC (P=2.44 × 10-8; odds ratio=66.8; 95% confidence interval, 19.8-225.0). rs9263726 in PSORS1C1, also significantly associated with allopurinol-related SJS/TEN, is in absolute linkage disequilibrium with human leukocyte antigen-B*5801, which is in strong association with allopurinol-induced SJS/TEN. The ease of typing rs9263726 makes it a useful biomarker for allopurinol-related SJS/TEN in Japanese.

AB - Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe, cutaneous adverse drug reactions that are rare but life threatening. Genetic biomarkers for allopurinol-related SJS/TEN in Japanese were examined in a genome-wide association study in which Japanese patients (n=14) were compared with ethnically matched healthy controls (n=991). Associations between 890 321 single nucleotide polymorphisms and allopurinol-related SJS/TEN were analyzed by the Fisher's exact test (dominant genotype mode). A total of 21 polymorphisms on chromosome 6 were significantly associated with allopurinol-related SJS/TEN. The strongest association was found at rs2734583 in BAT1, rs3094011 in HCP5 and GA005234 in MICC (P=2.44 × 10-8; odds ratio=66.8; 95% confidence interval, 19.8-225.0). rs9263726 in PSORS1C1, also significantly associated with allopurinol-related SJS/TEN, is in absolute linkage disequilibrium with human leukocyte antigen-B*5801, which is in strong association with allopurinol-induced SJS/TEN. The ease of typing rs9263726 makes it a useful biomarker for allopurinol-related SJS/TEN in Japanese.

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A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients

Abstract

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