+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Chemotherapeutic drug susceptibility associated SNPs are enriched in expression quantitative trait loci

, : Chemotherapeutic drug susceptibility associated SNPs are enriched in expression quantitative trait loci. Proceedings of the National Academy of Sciences of the United States of America 107(20): 9287-9292

Pharmacogenomics has employed candidate gene studies and, more recently, genome-wide association studies (GWAS) in efforts to identify loci associated with drug response and/or toxicity. The advantage of GWAS is the simultaneous, unbiased testing of millions of SNPs; the challenge is that functional information is absent for the vast majority of loci that are implicated. In the present study, we systematically evaluated SNPs associated with chemotherapeutic agent-induced cytotoxicity for six different anticancer agents and evaluated whether these SNPs were disproportionately likely to be within a functional class such as coding (consisting of missense, nonsense, or frameshift polymorphisms), noncoding (such as 3'UTRs or splice sites), or expression quantitative trait loci (eQTLs; indicating that a SNP genotype is associated with the transcript abundance level of a gene). We found that the chemotherapeutic drug susceptibility-associated SNPs are more likely to be eQTLs, and, in fact, more likely to be associated with the transcriptional expression level of multiple genes (n > or = 10) as potential master regulators, than a random set of SNPs in the genome, conditional on minor allele frequency. Furthermore, we observed that this enrichment compared with random expectation is not present for other traditionally important coding and noncoding SNP functional categories. This research therefore has significant implications as a general approach for the identification of genetic predictors of drug response and provides important insights into the likely function of SNPs identified in GWAS analysis of pharmacologic studies.


PMID: 20442332

DOI: 10.1073/pnas.1001827107

Other references

Kapoor, V.K., 1992: Vascular lesions in abdominal tuberculosis. Indian Journal of Gastroenterology 11(2): 99-99

Ueno, N.; Tomiyama, T.; Tano, S.; Wada, S.; Miyata, T., 1997: Color Doppler ultrasound guidance for needle biopsy of pancreatic lesions. Journal of Clinical Ultrasound 25(8): 461-461

Ono, T.; Li, C.; Mizutani, E.; Terashita, Y.; Yamagata, K.; Wakayama, T., 2011: Inhibition of class IIb histone deacetylase significantly improves cloning efficiency in mice. Since the first mouse clone was produced by somatic cell nuclear transfer, the success rate of cloning in mice has been extremely low. Some histone deacetylase inhibitors, such as trichostatin A and scriptaid, have improved the full-term developme...

Warren, G., 2014: Transport through the Golgi in Trypanosoma brucei. The mechanism of transport through the Golgi is still controversial, and this has led to a search for model organisms that might provide new insights. One such is the protozoan parasite, <em>Trypanosoma brucei</em>, which has a single...

Sampaio, J.M.M.; Rodrigues, J.A.S., 1980: The active mango germplasm bank. The 92 varieties represented in the collection are named, as well as the ten varieties most commonly cultivated in the northern, north-western and west-central regions of Brazil and the ten most popular in the south-east. Data on fruit quality fea...

Boulos B.M.; Davis Le; Larks S.D.; Larks G.G.; Sirtori C.R.; Almond C.H., 1971: Placental transfer of drugs part 4 placental transfer of chlorpromazine pento barbital and phenyl butazone with fetal electro cardiographic changes as determined by direct lead tracing. Archives Internationales de Pharmacodynamie et de Therapie 194(2): 403-414

Weissmann, L.; Podmanická, D., 1970: Influence of nutrition and breeding temperature on the lenght of larval development of Scotia segetum Den. et Schiff. Biologia 25(8): 537-545

Swietek, N.; Waldert, M.; Susani, M.; Schatzl, G.; Klatte, T., 2013: Intravesical bacillus Calmette-Guérin instillation therapy for non-muscle-invasive bladder cancer following solid organ transplantation. Solid organ recipients have a substantial risk of developing bladder cancer, with high-risk non-muscle-invasive bladder cancer (NMIBC) being the most frequent diagnosis. Theoretically, adjuvant bacillus Calmette-Guérin (BCG) therapy is contraindi...

Dengler, H.; Reichel, G., 1957: Effect of a decarboxylase inhibitor on the effects of dopa & dops on blood pressure. Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie 232(1): 324-326

Dykin, V.I.; Ivanishchev, K.V.; Kornev, N.P.; Mikheev, A.A.; Solomakha, V.N., 2014: A device for calibration of the dynamic tonometer TVGD-01. Meditsinskaia Tekhnika: 33-36