title: Genetic variants of OCT1 influence glycemic response to metformin in Han Chinese patients with type-2 diabetes mellitus in Shanghai.
abstract: OBJECTIVE
  Genetic variation in OCT1 can influence the glycemic response to metformin. We evaluated the effects of the OCT1 single-nucleotide polymorphisms (SNPs), rs1867351, rs4709400, rs628031, and rs2297374, on metformin efficacy in type-2 diabetes mellitus (DM) patients.
  
  
  METHODS
  We performed a single-center prospective analysis of the distributions of these SNPs in a cohort of Han Chinese subjects in Shanghai, China (HCS), and evaluated the effects of each SNP on glycemic control in HCS DM patients following 3 months of incident metformin treatment.
  
  
  RESULTS
  The allele frequencies of rs4709400 and rs628031 in our HCS control group differed from those previously reported for Han Chinese subjects in Beijing (HCB), as well as those previously reported for Caucasians and Africans, whereas the allele frequencies of rs1867351 and rs2297374 were more similar to those in HCB subjects. The DM patients with the rs1867351 T/T or rs4709400 G/G genotype exhibited greater reductions in postprandial plasma glucose (PPG), compared to those with different genotypes of these SNPs. The DM patients with the rs2297374 C/T, rs4709400 G/G, or rs628031 G/G genotype exhibited greater reductions in fasting plasma glucose (FPG), and those with the rs1867351 T/T, rs628031 A/A, or rs2297374 C/T genotype exhibited greater reductions in HbA1c , compared to those with different genotypes of these SNPs. Conclusions /interpretation: The rs1867351, rs4709400, rs628031, and rs2297374 SNPs of OCT1 have selective effects on FPG, PPG, and HbA1c in HCS DM patients in response to metformin treatment. Future studies of these SNPs in larger samples of HCS DM patients are warranted.
authors.affiliation: Department of Endocrinology, Dahua Hospital Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology, Dahua Hospital Shanghai, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Endocrinology, Dahua Hospital Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Dahua Hospital Shanghai, China.
authors.forename: Zhikui
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology, Dahua Hospital Shanghai, China.
authors.forename: Xiangying
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Endocrinology, Dahua Hospital Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Department of Endocrinology, Dahua Hospital Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, Dahua Hospital Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yan
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001786:Blood Glucose; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D027702:Organic Cation Transporter 1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D027702:Organic Cation Transporter 1; D008687:Metformin
keywords: OCT1; Type-2 diabetes mellitus; glycemic control; metformin; polymorphism