Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent

被引：32

作者：

Aminkeng, F. ^{[1
]}

Ross, C. J. D. ^{[2
]}

Rassekh, S. R. ^{[3
]}

Brunham, L. R. ^{[1
,4
,5
]}

Sistonen, J. ^{[1
,6
,7
]}

Dube, M-P ^{[8
,9
]}

Ibrahim, M. ^{[10
]}

Nyambo, T. B. ^{[11
]}

Omar, S. A. ^{[12
]}

Froment, A. ^{[13
]}

Bodo, J-M ^{[14
]}

Tishkoff, S. ^{[15
,16
]}

Carleton, B. C. ^{[2
]}

Hayden, M. R. ^{[1
,4
,5
]}

机构：

[1] Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada

[2] Univ British Columbia, Div Translat Therapeut, Dept Pediat, Vancouver, BC V5Z 4H4, Canada

[3] Univ British Columbia, Div Pediat Hematol Oncol BMT, Dept Pediat, Vancouver, BC V5Z 4H4, Canada

[4] Natl Univ Singapore, Translat Lab Genet Med, Dept Med, Singapore 117548, Singapore

[5] Assoc Sci Technol & Res A STAR, Singapore, Singapore

[6] Univ Hosp Bern, Inselspital, CH-3010 Bern, Switzerland

[7] Univ Bern, Bern, Switzerland

[8] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada

[9] Univ Montreal, Montreal, PQ, Canada

[10] Univ Khartoum, Dept Mol Biol, Inst Endem Dis, Khartoum, Sudan

[11] Muhimbili Univ Hlth & Allied Sci, Dept Biochem, Dar Es Salaam, Tanzania

[12] Kenya Govt Med Res Ctr, Ctr Biotechnol Res & Dev, Nairobi, Kenya

[13] Musee Homme Paris, UMR 208, IRD MNHN, Paris, France

[14] Minist Rech Sci & Innovat, Yaounde, Cameroon

[15] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA

[16] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA

来源：

PHARMACOGENOMICS JOURNAL | 2014年 / 14卷 / 02期

基金：

加拿大健康研究院; 加拿大创新基金会;

关键词：

pharmacogenomic diversity; genetic ancestry; drug response; ADRs; ACUTE LYMPHOBLASTIC-LEUKEMIA; SINGLE-NUCLEOTIDE POLYMORPHISMS; THIOPURINE S-METHYLTRANSFERASE; CHILDHOOD-CANCER; CISPLATIN CHEMOTHERAPY; INDUCED CARDIOTOXICITY; HEART-FAILURE; BREAST-CANCER; CHILDREN; TOXICITY;

D O I：

10.1038/tpj.2013.13

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

There is established clinical evidence for differences in drug response, cure rates and survival outcomes between different ethnic populations, but the causes are poorly understood. Differences in frequencies of functional genetic variants in key drug response and metabolism genes may significantly influence drug response differences in different populations. To assess this, we genotyped 1330 individuals of African (n=372) and European (n=958) descent for 4535 single-nucleotide polymorphisms in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Important and remarkable differences in the distribution of genetic variants were observed between Africans and Europeans and among the African populations. These could translate into significant differences in drug efficacy and safety profiles, and also in the required dose to achieve the desired therapeutic effect in different populations. Our data points to the need for population-specific genetic variation in personalizing medicine and care.

引用

页码：160 / 170

页数：11

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