Browsing by Author "Kim, S."

Now showing 1 - 3 of 3
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    Cytochrome P450 2D6 activity predicts discontinuation of tamoxifen therapy in breast cancer patients
    (Springer Nature, 2009-08) Rae, J. M.; Sikora, M. J.; Henry, N. L.; Li, L.; Kim, S.; Oesterreich, S.; Skaar, Todd C.; Nguyen, A. T.; Desta, Z.; Storniolo, A. M.; Flockhart, David A.; Hayes, D. F.; Stearns, V.
    The selective estrogen receptor modulator tamoxifen is routinely used for treatment and prevention of estrogen-receptor-positive breast cancer. Studies of tamoxifen adherence suggest that over half of patients discontinue treatment before the recommended 5 years. We hypothesized that polymorphisms in CYP2D6, the enzyme responsible for tamoxifen activation, predict for tamoxifen discontinuation. Tamoxifen-treated women (n=297) were genotyped for CYP2D6 variants and assigned a ‘score’ based on predicted allele activities from 0 (no activity) to 2 (high activity). Correlation between CYP2D6 score and discontinuation rates at 4 months was tested. We observed a strong nonlinear correlation between higher CYP2D6 score and increased rates of discontinuation (r2=0.935, P=0.018). These data suggest that presence of active CYP2D6 alleles may predict for higher likelihood of tamoxifen discontinuation. Therefore, patients who may be most likely to benefit from tamoxifen may paradoxically be most likely to discontinue treatment prematurely.
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    Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease
    (Nature Publishing Group, 2011-11) Furney, SJ; Simmons, A.; Breen, G.; Pedroso, I.; Lunnon, K.; Proitsi, P.; Hodges, A.; Powell, J.; Wahlund, L-O; Kloszewska, I.; Mecocci, P.; Soininen, H.; Tsolaki, M.; Vellas, B.; Spenger, C.; Lathrop, M.; Shen, L.; Kim, S.; Saykin, AJ; Weiner, MW; Lovestone, S.; Alzheimer's Disease Neuroimaging Initiative and the AddNeuroMed Consortium; Radiology and Imaging Sciences, School of Medicine
    Alzheimer's disease (AD) is a progressive neurodegenerative disorder with considerable evidence suggesting an initiation of disease in the entorhinal cortex and hippocampus and spreading thereafter to the rest of the brain. In this study, we combine genetics and imaging data obtained from the Alzheimer's Disease Neuroimaging Initiative and the AddNeuroMed study. To identify genetic susceptibility loci for AD, we conducted a genome-wide study of atrophy in regions associated with neurodegeneration in this condition. We identified one single-nucleotide polymorphism (SNP) with a disease-specific effect associated with entorhinal cortical volume in an intron of the ZNF292 gene (rs1925690; P-value=2.6 × 10(-8); corrected P-value for equivalent number of independent quantitative traits=7.7 × 10(-8)) and an intergenic SNP, flanking the ARPP-21 gene, with an overall effect on entorhinal cortical thickness (rs11129640; P-value=5.6 × 10(-8); corrected P-value=1.7 × 10(-7)). Gene-wide scoring also highlighted PICALM as the most significant gene associated with entorhinal cortical thickness (P-value=6.7 × 10(-6)).
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    Identification of functional variants from whole-exome sequencing, combined with neuroimaging genetics
    (Springer Nature, 2013) Nho, K.; Corneveaux, J. J.; Kim, S.; Lin, H.; Risacher, S. L.; Shen, L.; Swaminathan, S.; Ramanan, V. K.; Liu, Y.; Foroud, T.; Inlow, M. H.; Siniard, A. L.; Reiman, R. A.; Aisen, P. S.; Petersen, R. C.; Green, R. C.; Jack, C. R.; Weiner, M. W.; Baldwin, C. T.; Lunetta, K.; Farrer, L. A.; Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study; Furney, S. J.; Lovestone, S.; Simmons, A.; Mecocci, P.; Vellas, B.; Tsolaki, M.; Kloszewska, I.; Soininen, H.; AddNeuroMed Consortium; McDonald, B. C.; Farlow, M. R.; Ghetti, B.; Indiana Memory and Aging Study; Huentelman, M. J.; Saykin, A. J.; Alzheimer's Disease Neuroimaging Initiative (ADNI); Radiology and Imaging Sciences, School of Medicine