抄録
Objectives: We investigated the four polymorphisms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) genes that are related to the pharmacologically active sites of methotrexate for the treatment of rheumatoid arthritis in 102 healthy Japanese adults and assessed the possibility of ethnic and gender differences. Methods: Polymorphisms of MTHFR C677T, A1298C, the two or three 28-bp tandem repeats in the TYMS 5′-untranslated regions (UTR), and the 6-bp deletion/insertion in the TYMS 3′-UTR were measured using polymerase chain reaction with restriction fragment length polymorphism method. Published data on allelic frequencies by ethnic group and gender were collected from Medline. Results: Allelic frequencies in healthy Japanese adults were: MTHFR 677T allele 41%, MTHFR 1298C allele 22%, TYMS 5′-UTR 3R allele 84%, and TYMS 3′-UTR-6-bp allele 59%. Significant differences were found in the distribution of MTHFR C677T between black and Japanese populations, of TYMS 5′-UTR alleles between Caucasian or black and Japanese populations, and of TYMS 3′-UTR alleles between Caucasian and Japanese populations (p < 0.001). Moreover, a gender difference was found in TYMS 3′-UTR allelic frequency in Japanese (p = 0.015). Conclusion: Ethnic and gender variations in the distribution of these allelic frequencies may associate with the difference in the effects of methotrexate in rheumatoid arthritis patients.
元の言語 | English |
---|---|
ページ(範囲) | 41-47 |
ページ数 | 7 |
ジャーナル | Pharmacogenomics |
巻 | 8 |
発行部数 | 1 |
DOI | |
出版物ステータス | Published - 2007 1 |
外部発表 | Yes |
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ASJC Scopus subject areas
- Pharmacology
- Genetics(clinical)
これを引用
Pharmacogentic study of methyleneterahyrofolate reductase and thymidylate synthase in Japanese and assessment of ethnic and gender differences. / Inoue, Sachie; Hashiguchi, Masayuki; Chiyoda, Takeshi; Sunami, Yukiko; Tanaka, Takanori; Mochizuki, Mayumi.
:: Pharmacogenomics, 巻 8, 番号 1, 01.2007, p. 41-47.研究成果: Article
}
TY - JOUR
T1 - Pharmacogentic study of methyleneterahyrofolate reductase and thymidylate synthase in Japanese and assessment of ethnic and gender differences
AU - Inoue, Sachie
AU - Hashiguchi, Masayuki
AU - Chiyoda, Takeshi
AU - Sunami, Yukiko
AU - Tanaka, Takanori
AU - Mochizuki, Mayumi
PY - 2007/1
Y1 - 2007/1
N2 - Objectives: We investigated the four polymorphisms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) genes that are related to the pharmacologically active sites of methotrexate for the treatment of rheumatoid arthritis in 102 healthy Japanese adults and assessed the possibility of ethnic and gender differences. Methods: Polymorphisms of MTHFR C677T, A1298C, the two or three 28-bp tandem repeats in the TYMS 5′-untranslated regions (UTR), and the 6-bp deletion/insertion in the TYMS 3′-UTR were measured using polymerase chain reaction with restriction fragment length polymorphism method. Published data on allelic frequencies by ethnic group and gender were collected from Medline. Results: Allelic frequencies in healthy Japanese adults were: MTHFR 677T allele 41%, MTHFR 1298C allele 22%, TYMS 5′-UTR 3R allele 84%, and TYMS 3′-UTR-6-bp allele 59%. Significant differences were found in the distribution of MTHFR C677T between black and Japanese populations, of TYMS 5′-UTR alleles between Caucasian or black and Japanese populations, and of TYMS 3′-UTR alleles between Caucasian and Japanese populations (p < 0.001). Moreover, a gender difference was found in TYMS 3′-UTR allelic frequency in Japanese (p = 0.015). Conclusion: Ethnic and gender variations in the distribution of these allelic frequencies may associate with the difference in the effects of methotrexate in rheumatoid arthritis patients.
AB - Objectives: We investigated the four polymorphisms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) genes that are related to the pharmacologically active sites of methotrexate for the treatment of rheumatoid arthritis in 102 healthy Japanese adults and assessed the possibility of ethnic and gender differences. Methods: Polymorphisms of MTHFR C677T, A1298C, the two or three 28-bp tandem repeats in the TYMS 5′-untranslated regions (UTR), and the 6-bp deletion/insertion in the TYMS 3′-UTR were measured using polymerase chain reaction with restriction fragment length polymorphism method. Published data on allelic frequencies by ethnic group and gender were collected from Medline. Results: Allelic frequencies in healthy Japanese adults were: MTHFR 677T allele 41%, MTHFR 1298C allele 22%, TYMS 5′-UTR 3R allele 84%, and TYMS 3′-UTR-6-bp allele 59%. Significant differences were found in the distribution of MTHFR C677T between black and Japanese populations, of TYMS 5′-UTR alleles between Caucasian or black and Japanese populations, and of TYMS 3′-UTR alleles between Caucasian and Japanese populations (p < 0.001). Moreover, a gender difference was found in TYMS 3′-UTR allelic frequency in Japanese (p = 0.015). Conclusion: Ethnic and gender variations in the distribution of these allelic frequencies may associate with the difference in the effects of methotrexate in rheumatoid arthritis patients.
KW - 5,10-methlenetetrahydrofolate reductase
KW - Allelic frequency
KW - Ethic difference
KW - Gender difference
KW - Genotype
KW - Methotrexate
KW - Polymorphism
KW - Thymidlate synthase
UR - http://www.scopus.com/inward/record.url?scp=33846557901&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846557901&partnerID=8YFLogxK
U2 - 10.2217/14622416.8.1.41
DO - 10.2217/14622416.8.1.41
M3 - Article
C2 - 17187508
AN - SCOPUS:33846557901
VL - 8
SP - 41
EP - 47
JO - Pharmacogenomics
JF - Pharmacogenomics
SN - 1462-2416
IS - 1
ER -