Genetic risk factors for VIPN in childhood acute lymphoblastic leukemia patients identified using whole-exome sequencing

被引：26

作者：

Abaji, Rachid ^{[1
,2
]}

Ceppi, Francesco ^{[3
,4
]}

Patel, Swati ^{[1
]}

Gagne, Vincent ^{[1
]}

Xu, Chang J. ^{[1
]}

Spinella, Jean-Francois ^{[1
]}

Colombini, Antonella ^{[5
]}

Parasole, Rosanna ^{[6
]}

Buldini, Barbara ^{[7
]}

Basso, Giuseppe ^{[7
]}

Conter, Valentino ^{[5
]}

Cazzaniga, Giovanni ^{[8
]}

Leclerc, Jean-Marie ^{[1
,9
]}

Laverdiere, Caroline ^{[1
,9
]}

Sinnett, Daniel ^{[1
,9
]}

Krajinovic, Maja ^{[1
,2
,8
]}

机构：

[1] CHU St Justine Res Ctr, Charles Bruneau Canc Ctr, Montreal, PQ H3T 1C5, Canada

[2] Univ Montreal, Dept Pharmacol & Physiol, Fac Med, Montreal, PQ H3C 3J7, Canada

[3] Univ Hosp Lausanne, Dept Woman Mother Child, Div Pediat, Pediat Hematol Oncol Unit, CH-1004 Lausanne, Switzerland

[4] Univ Hosp Lausanne, Dept Woman Mother Child, Div Pediat, Pediat Hematol Oncol Res Lab, CH-1004 Lausanne, Switzerland

[5] Univ Milano Bicocca, Dept Pediat, Osped S Gerardo, I-20835 Monza, Italy

[6] Santobono Pausilipon Hosp, Dept Pediat Hematooncol, I-80129 Naples, Italy

[7] Univ Padua, Dept Woman & Child Hlth, Lab Haematol Oncol, I-35128 Padua, Italy

[8] Univ Milano Bicocca, Dept Pediat, Ctr Ric Tettamanti, I-20835 Monza, Italy

[9] Univ Montreal, Dept Pediat, Fac Med, Montreal, PQ H4A 3J1, Canada

来源：

PHARMACOGENOMICS | 2018年 / 19卷 / 15期

基金：

加拿大健康研究院;

关键词：

acute lymphoblastic leukemia; adverse drug reactions; association study; cancer; genetics; pharmacogenetics; polymorphism; vincristine-induced peripheral neuropathy; whole-exome sequencing; INDUCED PERIPHERAL NEUROPATHY; MARIE-TOOTH DISEASE; MUSCULAR-DYSTROPHY; VINCRISTINE PHARMACOKINETICS; AXONAL NEUROPATHY; CHILDREN; NEUROTOXICITY; POLYMORPHISMS; ASSOCIATION; TOXICITY;

D O I：

10.2217/pgs-2018-0093

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aim: To identify genetic markers associated with vincristine-induced peripheral neuropathy (VIPN) in childhood acute lymphoblastic leukemia. Patients & methods: Whole-exome sequencing data were combined with exome-wide association study to identify predicted-functional germline variants associated with high-grade VIPN. Genotyping was then performed for top-ranked signals (n =237), followed by validation in independent replication group (n =405). Results: Minor alleles of rs2781377/SYNE2 (p=0.01) and rs10513762/MRPL47 (p=0.01) showed increased risk, whereas that of rs3803357/BAHD1 had a protective effect (p=0.007). Using a genetic model based on weighted genetic risk scores, an additive effect of combining these loci was observed (p=0.003). The addition of rs1135989/ACTG1 further enhanced model performance (p=0.0001). Conclusion: Variants in SYNE2, MRPL47 and BAHD1 genes are putative new risk factors for VIPN in childhood acute lymphoblastic leukemia.

引用

页码：1181 / 1193

页数：13

共 55 条

[11] Vincristine pharmacogenomics: 'winner's curse' or a different phenotype? [J].

Diouf, Barthelemy ;

Crews, Kristine R. ;

Evans, William E. .

PHARMACOGENETICS AND GENOMICS, 2016, 26 (02) :51-52

[12] Association of an Inherited Genetic Variant With Vincristine-Related Peripheral Neuropathy in Children With Acute Lymphoblastic Leukemia [J].

Diouf, Barthelemy ;

Crews, Kristine R. ;

Lew, Glen ;

Pei, Deqing ;

Cheng, Cheng ;

Bao, Ju ;

Zheng, Jie J. ;

Yang, Wenjian ;

Fan, Yiping ;

Wheeler, Heather E. ;

Wing, Claudia ;

Delaney, Shannon M. ;

Komatsu, Masaaki ;

Paugh, Steven W. ;

McCorkle, Joseph Robert ;

Lu, Xiaomin ;

Winick, Naomi J. ;

Carroll, William L. ;

Loh, Mignon L. ;

Hunger, Stephen P. ;

Devidas, Meenakshi ;

Pui, Ching-Hon ;

Dolan, M. Eileen ;

Relling, Mary V. ;

Evans, William E. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2015, 313 (08) :815-823

[13] A Cardio-Neurological Form of Laminopathy: Dilated Cardiomyopathy with Permanent Partial Atrial Standstill and Axonal Neuropathy [J].

Duparc, Alexandre ;

Cintas, Pascal ;

Somody, Elisabeth ;

Bieth, Eric ;

Richard, Pascale ;

Maury, Philippe ;

Delay, Marc .

PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY, 2009, 32 (03) :410-415

[14] Increased Risk of Vincristine Neurotoxicity Associated With Low CYP3A5 Expression Genotype in Children With Acute Lymphoblastic Leukemia [J].

Egbelakin, Akinbode ;

Ferguson, Michael J. ;

MacGill, Emily A. ;

Lehmann, Amalia S. ;

Topletz, Ariel R. ;

Quinney, Sara K. ;

Li, Lang ;

McCammack, Kevin C. ;

Hall, Stephen D. ;

Renbarger, Jamie L. .

PEDIATRIC BLOOD & CANCER, 2011, 56 (03) :361-367

[15] A new mutation of the lamin A/C gene leading to autosomal dominant axonal neuropathy, muscular dystrophy, cardiac disease, and leuconychia [J].

Goizet, C ;

Ben Yaou, R ;

Demay, L ;

Richard, P ;

Bouillot, S ;

Rouanet, M ;

Hermosilla, E ;

Le Masson, G ;

Lagueny, A ;

Bonne, G ;

Ferrer, X .

JOURNAL OF MEDICAL GENETICS, 2004, 41 (03)

[16]

Gtex Portal, GEN T2SS EXPR GTEX P

[17]

Gutierrez-Camino A, 2017, PHARMACOGENOMICS J, DOI 10. 1038/s41397-017-0003-3

[18] Lack of association of the CEP72 rs924607 TT genotype with vincristine-related peripheral neuropathy during the early phase of pediatric acute lymphoblastic leukemia treatment in a Spanish population [J].

Gutierrez-Camino, Angela ;

Martin-Guerrero, Idoia ;

Lopez-Lopez, Elixabet ;

Echebarria-Barona, Aizpea ;

Zabalza, Inaki ;

Ruiz, Irune ;

Guerra-Merino, Isabel ;

Garcia-Orad, Africa .

PHARMACOGENETICS AND GENOMICS, 2016, 26 (02) :100-102

[19]

HAIM N, 1994, CANCER, V73, P2515, DOI 10.1002/1097-0142(19940515)73:10<2515::AID-CNCR2820731011>3.0.CO

[20]

2-G

← 1 2 3 4 5 6 →