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Cytosolic 5’-nucleotidaseⅡlike 1（NT5C2L1） gene sequence variation and functional genomics:cytosine arabinoside and gemcitabine pharmacogenetics

Cytosolic 5’-nucleotidaseⅡlike 1（NT5C2L1） gene sequence ...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： pinar aksoy Krishna R.Kalari Irene Moon Linda L.Pelleymounter Bruce W Eckloff Eric D.Wieben Richard M.Weinshilboum Department of Molecular Pharmacology and Experimental Therapeutics Department of Biochemistry and Molecular Biology Mayo Clinic RochesterMNUSA

＜正＞Background:5’-Nucleotidases play a critical role in nucleotide pool balance and the metabolism of nucleoside analogs such as gemcitabine and cytosine arabinoside（AraC）.Previously study performed an expression array association study with gemcitabine and AraC cytotoxicity using 288 human lymphoblastoid cell lines. One gene that was significantly associated with gemcitabine cytotoxicity was a nucleotidase family member,NT5C2L1. Very little is known with regard to the pharmacogenomics of this ***:We set out to identify common genetic variation in NT5C2L1 by resequencing the gene and to determine the effect of that variation on NT5C2L1 protein function and response to cytidine *** resequencing 288 ethnically defined DNA samples,we identified 61 NT5C2L1 polymorphisms,41 of which were *** studies were performed with four nonsynonymous（Gly152Asp,Ile162Val,Asn210Ile,Asn432Ser） and 2 synonymous cSNPs（G112A,T25A） as well as NT5C2L1 wild ***:Nucleotidase kinetic analysis showed IMP,CMP,AMP,GMP AraCMP and GemMP were substrates of *** is no phosphotransferase ***5CL21 knockdown made Su86 cell more insistent to the *** variation constructs showed no difference of enzyme activity and protein compare with the wild *** association study between SNPs and NT5C2L1 expression in the 288 cell lines from which DNA was extracted to resequence NT5C2L1 identified 4 SNPs that were significantly associated with NT5C2L1 *** showed that two of those SNPs,13（-25） and 16（112） didn’t alter DNA-protein binding *** findings increase our knowledge of common genetic variation in NT5C2L1 and their effect on *** may also help to shed light on future translational pharmacogenomic studies of nucleoside analog drugs.

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