Genetic Association of PARP15 Polymorphisms with Clinical Outcome of Acute Myeloid Leukemia in a Korean Population.
OBJECTIVE
Some members of the poly ADP-ribose polymerase (PARP) protein family have been regarded as targets for the therapeutic inhibition of cancer. Among these PARP genes, poly ADP-ribose polymerase family, member 15 (PARP15) is a candidate gene for cancer development due to its ability to regulate gene transcription and its reported association with apoptosis. The current study investigated the possible association between PARP15 single-nucleotide polymorphisms and the risk of acute myeloid leukemia (AML). In addition, we analyzed the effects of the PARP15 polymorphisms on the clinical phenotypes associated with cytosine arabinose (AraC) chemotherapy in AML patients.


METHODS
Ten PARP15 polymorphisms were genotyped via TaqMan assay in a total of 344 Korean subjects, including 103 AML patients and 241 normal controls. The genetic effects of the polymorphisms on the risk of AML and the clinical phenotypes were analyzed using Statistical Analysis System (SAS) software.


RESULTS
The results from a Cox regression analysis for overall survival revealed that two polymorphisms were associated with increased overall survival and the signal for rs17208928 was retained after correcting for multiple tests (pcorr< 0.05).


CONCLUSIONS
These results suggest the possibility that the PARP15 gene may be a potential therapeutic target in AML patients although much larger scale studies are needed for validation.
1 Department of Life Science, Sogang University , Seoul, Republic of Korea.
Min Kyung
MK
Lee
2 Cancer Research Institute, Seoul National University Hospital , Seoul, Republic of Korea.|3 Department of Genetic Epidemiology, SNP Genetics, Inc. , Seoul, Republic of Korea.
Hyun Sub
HS
Cheong
4 Department of Internal Medicine, Seoul National University College of Medicine , Seoul, Republic of Korea.
Youngil
Y
Koh
5 Functional Genome Institute , PDXen Biosystem, Inc., Seoul, Republic of Korea.
Kwang-Sung
KS
Ahn
2 Cancer Research Institute, Seoul National University Hospital , Seoul, Republic of Korea.|4 Department of Internal Medicine, Seoul National University College of Medicine , Seoul, Republic of Korea.|6 Clinical Research Institute, Seoul National University Hospital , Seoul, Republic of Korea.
Sung-Soo
SS
Yoon
1 Department of Life Science, Sogang University , Seoul, Republic of Korea.|3 Department of Genetic Epidemiology, SNP Genetics, Inc. , Seoul, Republic of Korea.
Hyoung Doo
HD
Shin
D036002:ADP Ribose Transferases / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012307:Risk Factors; D016896:Treatment Outcome
D036002:ADP Ribose Transferases; C584563:PARP15 protein, human
PARP15; acute myeloid leukemia; cytosine arabinoside; single nucleotide polymorphism