Genetic predictors of glucocorticoid-induced hypertension in children with acute lymphoblastic leukemia

被引:35
作者
Kamdem, Landry K. [1 ]
Hamilton, Leo [1 ,3 ]
Cheng, Cheng [2 ]
Liu, Wei [2 ]
Yang, Wenjiang [1 ]
Johnson, Julie A. [5 ]
Pui, Ching-Hon [3 ,4 ]
Relling, Mary V. [1 ]
机构
[1] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA
[2] St Jude Childrens Hosp, Dept Biostat, Memphis, TN 38105 USA
[3] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA
[4] Univ Tennessee, Memphis, TN USA
[5] Univ Florida, Ctr Pharmacogenet, Coll Pharm, Gainesville, FL USA
关键词
acute lymphoblastic leukemia; glucocorticoids; hypertension; single nucleotide polymorphism;
D O I
10.1097/FPC.0b013e3282fc5801
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Objective Glucocorticoids are used universally in the remission induction therapy for acute lymphoblastic leukemia (ALL). One of the adverse effects of glucocorticoids is hypertension. Our aim was to define the frequency of and clinical and genetic risk factors for steroid-induced hypertension. Methods We determined the genotypes for 203 candidate polymorphisms in genes previously linked to hypertension or to the pharmacokinetics or pharmacodynamics of antileukemic agents. Hypertension was defined according to the guidelines of the American Academy of Pediatrics; patients were evaluated during the 28-day period of prednisone at 40 mg/m(2)/day during remission induction of childhood ALL. Results Of the 602 children with newly diagnosed ALL who were normotensive pretherapy, 270 (45%) developed hypertension during remission induction. None of the putative risk factors (age, sex, race, white blood cell count, risk group, body mass index, or serum creatinine) was associated with hypertension. Among the polymorphisms genotyped, we identified eight genes (CNTNAP2, LEPR, CRHR1, NTAN1, SLC12A3, ALPL, BGLAP, and APOB) containing variants that were associated with hypertension (chi(2) P values 0.002-0.048), several of which interact with the hypothalamus-pituitary-adrenal axis. Polymorphisms in CYP3A4 and CYP3A5 were not associated with hypertension. Conclusion Hypertension is common during ALL remission induction and is related to germline genetic variation.
引用
收藏
页码:507 / 514
页数:8
相关论文
共 50 条
[1]   HIGH-INCIDENCE OF HYPERTENSION IN CHILDREN PRESENTING WITH ACUTE LYMPHOBLASTIC-LEUKEMIA [J].
ATTARDMONTALTO, SP ;
SAHA, V ;
NG, YY ;
KINGSTON, JE ;
EDEN, OB .
PEDIATRIC HEMATOLOGY AND ONCOLOGY, 1994, 11 (05) :519-525
[2]   Dexamethasone-associated toxicity during induction chemotherapy for childhood acute lymphoblastic leukemia is augmented by concurrent use of daunomycin [J].
Belgaumi, AF ;
Al-Bakrah, M ;
Al-Mahr, M ;
Al-Jefri, A ;
Al-Musa, A ;
Saleh, M ;
Salim, MF ;
Osman, M ;
Osman, L ;
El-Solh, H .
CANCER, 2003, 97 (11) :2898-2903
[3]   An afferent vagal nerve pathway links hepatic PPARα activation to glucocorticoid-induced insulin resistance and hypertension [J].
Bernal-Mizrachi, Carlos ;
Liu Xiaozhong ;
Li Yin ;
Knutsen, Russell H. ;
Howard, Michael J. ;
Arends, Joop J. A. ;
DeSantis, Pascual ;
Coleman, Trey ;
Semenkovich, Clay F. .
CELL METABOLISM, 2007, 5 (02) :91-102
[4]   Association of CYP3A5 genotypes with blood pressure and renal function in African families [J].
Bochud, Murielle ;
Eap, Chin B. ;
Elston, Robert C. ;
Bovet, Pascal ;
Maillard, Marc ;
Schild, Laurent ;
Shamlaye, Conrad ;
Burnier, Michel .
JOURNAL OF HYPERTENSION, 2006, 24 (05) :923-929
[5]   Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group [J].
Bostrom, BC ;
Sensel, MR ;
Sather, HN ;
Gaynon, PS ;
La, MK ;
Johnston, K ;
Erdmann, GR ;
Gold, S ;
Heerema, NA ;
Hutchinson, RJ ;
Provisor, AJ ;
Trigg, ME .
BLOOD, 2003, 101 (10) :3809-3817
[6]  
Bydlowski SP, 1996, BRAZ J MED BIOL RES, V29, P1269
[7]  
CHENG C, 2004, STAT APPL GENET MOL, V3
[8]   Corticotropin-releasing hormone and its receptors: an evaluation at the transcription level in vivo [J].
Drolet, G ;
Rivest, S .
PEPTIDES, 2001, 22 (05) :761-767
[9]   Hypertension in blacks [J].
Fauvel, Jean-Pierre ;
Laville, Maurice .
PRESSE MEDICALE, 2006, 35 (06) :1067-1071
[10]   Cortisol and the renal handling of electrolytes: role in glucocorticoid-induced hypertension and bone disease [J].
Ferrari, P .
BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 17 (04) :575-589