| Autor: |
Diabetes Prevention Program Research Group, Jose C. Florez, Toni I. Pollin, William C. Knowler, Steven E. Kahn, Robert L. Hanson, Paul W. Franks, L. Keoki Williams, Shujie Xiao, Adriana M. Hung, Ayush Giri, Kathleen M. Giacomini, Ewan R. Pearson, Sook Wah Yee, Adem Y. Dawed, Qing Pan, Josep M. Mercader, Maegan Harden, Jennifer N. Todd, Ling Chen, Shylaja Srinivasan, Kathleen A. Jablonski, James A. Perry, Josephine Li |
| Rok vydání: |
2023 |
| DOI: |
10.2337/figshare.21719837 |
| Popis: |
Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not replicated in the Diabetes Prevention Program (DPP). To assess pharmacogenetic interactions in pre-diabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in metformin (MET, n=876) and placebo (PBO, n=887) arms. Multiple linear regression assessed association with one-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal components. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes incidence. We identified four genome-wide significant variants after correcting for correlated traits (pENOSF1 (minor allele frequency [MAF]AFR=0.07, MAFEUR=0.002) was associated with an increase in % glycated hemoglobin (per minor allele β=0.39 [95% CI 0.28, 0.50], p=2.8×10-12). Rs145591055 near OMSR (MAF=0.10 in American Indians), was associated with weight loss (kg) (per G allele β=-7.55 [95% CI -9.88, -5.22], p=3.2×10-10) in MET. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants (p(G×T) |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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