title: A Common Susceptibility Gene for Type 2 Diabetes Is Associated with Drug Response to a DPP-4 Inhibitor: Pharmacogenomic Cohort in Okinawa Japan.
abstract: We investigated the association between common type 2 susceptibility variants of CDK5 regulatory subunit associated protein 1-like 1(CDKAL1) and therapeutic responses to anti-diabetic agents among patients with type 2 diabetes. Two SNPs (rs7754840: C>G, rs7756992: A>G) were genotyped via the Taqman PCR method. A total of 798 type 2 diabetic patients were included. HbA1c reduction after use of DPP-4 inhibitors for 3 months was significantly greater in patients with a risk allele for type 2 diabetes (GG -0.4%, CG -0.5%, CC -0.8%, p = 0.02 for rs7754840 and AA -0.4%, AG -0.5%, GG -0.8%, p = 0.01 for rs7756992). Linear regression analysis showed that per allele reductions of hemoglobin A1c (HbA1c) after 3 months were -0.10% for rs7754840 (p = 0.02) and -0.13% for rs7756992 (p = 0.0008) after adjusting for clinically influential covariates such as age, sex, BMI, duration of diabetes, baseline HbA1c and concomitant anti-diabetic agents. The results suggested that common variants of CDKAL1 are associated with therapeutic response to DPP-4 inhibitors.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus Graduate School of Medicine, Okinawa Japan.|Department of Diabetes, Endocrinology and Metabolism, Saiseikai Yokohama City Nanbu Hospital, Yokohama, Japan.
authors.forename: Uru Nezu
authors.initials: UN
authors.lastname: Osada
authors.affiliation: Sunawaga Medical Clinic, Okinawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sunagawa
authors.affiliation: Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus Graduate School of Medicine, Okinawa Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ueda
mesh_terms: D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D023281:Genomics; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D016896:Treatment Outcome; D012359:tRNA Methyltransferases / Q000235:genetics*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D012359:tRNA Methyltransferases; C517652:hemoglobin A1c protein, human; C525110:CDKAL1 protein, human