Development of a simple genotyping method for the HLA-A*31:01-tagging SNP in Japanese.
OBJECTIVE
To construct a simple, low-cost typing method for the surrogate marker of HLA-A*31:01, a risk factor for carbamazepine (CBZ) related Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).


METHODS
DNAs from Japanese SJS/TEN patients were used for genotyping and developing the assay.


RESULTS
HLA-A*31:01 was confirmed to be significantly associated with definite/probable cases of CBZ-related SJS/TEN (p = 0.0040). Three single nucleotide polymorphisms, rs1150738, rs3869066 and rs259945, were in absolute linkage disequilibrium with HLA-A*31:01 in 210 Japanese SJS/TEN patients. Robust genotyping of rs3869066 in ZNRD1-AS1 was developed using polymerase chain reaction-restriction fragment length polymorphism assays.


CONCLUSIONS
Single nucleotide polymorphism genotyping is less time consuming and cheaper than conventional HLA typing, and would be useful for identifying Japanese patients at risk of CBZ-related SJS/TEN.
Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Keiko
K
Maekawa
Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Ryosuke
R
Nakamura
Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Nahoko
N
Kaniwa
EBM Research Center, Kyoto University Graduate School of Medicine, Yoshida-Konoecho, Sakyo-ku, Kyoto 606-8501, Japan.
Seiho
S
Mizusawa
EBM Research Center, Kyoto University Graduate School of Medicine, Yoshida-Konoecho, Sakyo-ku, Kyoto 606-8501, Japan.
Aya
A
Kitamoto
EBM Research Center, Kyoto University Graduate School of Medicine, Yoshida-Konoecho, Sakyo-ku, Kyoto 606-8501, Japan.
Takuya
T
Kitamoto
Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Maho
M
Ukaji
Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Yumiko
Y
Matsuzawa
Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Emiko
E
Sugiyama
Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Yoshimi
Y
Uchida
Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.|Department of Food Science & Technology, Tokyo University of Marine Science & Technology, 4-5-7 Konan, Minato-ku, Tokyo 108-8477, Japan.
Kouichi
K
Kurose
Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-0841, Japan.|Department of Frontier Medical Science & Technology for Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-0841, Japan.
Mayumi
M
Ueta
Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-0841, Japan.
Chie
C
Sotozono
Shizuoka Institute of Epilepsy & Neurological Disorders, National Epilepsy Center, 886 Urushiyama, Aoi-ku, Shizuoka-shi, Shizuoka 420-8688, Japan.
Hiroko
H
Ikeda
Department of Dermatology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
Akiko
A
Yagami
Department of Environmental Immuno-dermatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0027, Japan.
Setsuko
S
Matsukura
Department of Frontier Medical Science & Technology for Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-0841, Japan.
Shigeru
S
Kinoshita
Molecular Epidemiology, Medical Research Institute, Tokyo Medical & Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-0034, Japan.
Masaaki
M
Muramatsu
Department of Environmental Immuno-dermatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0027, Japan.
Zenro
Z
Ikezawa
EBM Research Center, Kyoto University Graduate School of Medicine, Yoshida-Konoecho, Sakyo-ku, Kyoto 606-8501, Japan.|Center for Preventive Medical Science, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
Akihiro
A
Sekine
Department of Neurology, Kochi Medical School, Kochi University, Oko-cho Kohasu, Nankoku, Kochi 783-8505, Japan.
Hirokazu
H
Furuya
Shizuoka Institute of Epilepsy & Neurological Disorders, National Epilepsy Center, 886 Urushiyama, Aoi-ku, Shizuoka-shi, Shizuoka 420-8688, Japan.
Yukitoshi
Y
Takahashi
Department of Dermatology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
Kayoko
K
Matsunaga
Department of Environmental Immuno-dermatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0027, Japan.
Michiko
M
Aihara
Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Yoshiro
Y
Saito
D000927:Anticonvulsants / Q000009:adverse effects; D044466:Asian People / Q000235:genetics*; D002220:Carbamazepine / Q000009:adverse effects; D004247:DNA / Q000235:genetics; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics*; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D013262:Stevens-Johnson Syndrome / Q000453:epidemiology / Q000235:genetics*; D016896:Treatment Outcome
D000927:Anticonvulsants; D005819:Genetic Markers; D015234:HLA-A Antigens; C069527:HLA-A31 antigen; D002220:Carbamazepine; D004247:DNA
PCR-RFLP; Stevens–Johnson syndrome/toxic epidermal necrolysis; carbamazepine; screening test