دورية أكاديمية
Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP)
| العنوان: | Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP) |
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| المؤلفون: | Li, Josephine H., Perry, James A., Jablonski, Kathleen A., Srinivasan, Shylaja, Chen, Ling, Todd, Jennifer N., Harden, Maegan, Mercader, Josep M., Pan, Qing, Dawed, Adem Y., Yee, Sook Wah, Pearson, Ewan R., Giacomini, Kathleen M., Giri, Ayush, Hung, Adriana M., Xiao, Shujie, Williams, L. Keoki, Franks, Paul W., Hanson, Robert L., Kahn, Steven E., Knowler, William C., Pollin, Toni I., Florez, Jose C. |
| المصدر: | Diabetes; 72(8), pp 1161-1172 (2023) ; ISSN: 0012-1797 |
| بيانات النشر: | American Diabetes Association Inc. |
| سنة النشر: | 2023 |
| المجموعة: | Lund University Publications (LUP) |
| مصطلحات موضوعية: | Endocrinology and Diabetes |
| الوصف: | Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been repli-cated in the Diabetes Prevention Program (DPP). To as-sess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal compo-nents. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes inci-dence. We identified four genome-wide significant variants after correcting for correlated traits (P < 9 × 1029). In the MET arm, rs144322333 near ENOSF1 (minor al-lele frequency [MAF]AFR = 0.07; MAFEUR = 0.002) was associated with an increase in percentage of glycated hemoglobin (per minor allele, b = 0.39 [95% CI 0.28, 0.50]; P = 2.8 × 10212). rs145591055 near OMSR (MAF = 0.10 in American Indians) was associated with weight loss (kilograms) (per G allele, b = 27.55 [95% CI 29.88, 25.22]; P = 3.2 × 10210) in the MET arm. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants [P(G×T) < 1.0 × 1024 ]. Replication in individuals with diabetes did not yield significant findings. A GWAS for metformin response in prediabetes revealed novel ethnic-specific associations that require further investigation but may have implications for tailored therapy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://lup.lub.lu.se/record/9c6b3577-af2a-4937-9e0d-3125bd080e0eTest; http://dx.doi.org/10.2337/db22-0702Test; pmid:36525397; scopus:85151776838 |
| DOI: | 10.2337/db22-0702 |
| الإتاحة: | https://doi.org/10.2337/db22-0702Test https://lup.lub.lu.se/record/9c6b3577-af2a-4937-9e0d-3125bd080e0eTest |
| رقم الانضمام: | edsbas.984DF5F4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.2337/db22-0702 |
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