title: Joint effects of diabetic-related genomic loci on the therapeutic efficacy of oral anti-diabetic drugs in Chinese type 2 diabetes patients.
abstract: Previous pharmacogenomic studies of oral anti-diabetic drugs have primarily focused on the effect of a single site. This study aimed to examine the joint effects of multiple loci on repaglinide or rosiglitazone efficacy in newly diagnosed type 2 diabetes mellitus (T2DM) patients. A total of 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks. The reductions in fasting glucose (ΔFPG), 2h glucose (Δ2hPG) and glycated hemoglobin (ΔHbA1c) levels were significantly associated with genetic score that was constructed using the sum of the effect alleles both in the repaglinide (P = 0.0011, 0.0002 and 0.0067, respectively) and rosiglitazone cohorts (P = 0.0002, 0.0014 and 0.0164, respectively) after adjusting for age, gender, body mass index and dosage. Survival analyses showed a trend towards a greater attainment rate of target HbA1c level in individuals with a high genetic score in the repaglinide cohort and rosiglitazone cohort (Plog-rank = 0.0815 and 0.0867, respectively) when the attainment of treatment targets were defined as more than 20% decrease of FPG, 2hPG, and HbA1c levels after treatment. In conclusion, we identified the joint effects of several T2DM-related loci on the efficacy of oral anti-diabetic drugs; moreover, we built a model to predict the drug efficacy.
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Chen
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Peng
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.|Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, 6600 Nanfeng Road, Shanghai, 201499, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Hu
authors.affiliation: Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002219:Carbamates / Q000627:therapeutic use; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D004334:Drug Administration Schedule; D005260:Female; D056426:Genetic Loci; D005838:Genotype; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D002219:Carbamates; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010880:Piperidines; D000077154:Rosiglitazone; D045162:Thiazolidinediones; C072379:repaglinide