Journal
DIABETES RESEARCH AND CLINICAL PRACTICE
Volume 109, Issue 1, Pages 57-63Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.diabres.2015.05.003
Keywords
SLC47A1; rs2289669 G > A variants; MATE 1; Metformin; Type 2 diabetes
Categories
Funding
- National Natural Science Foundation of China [81070650, 81270397]
Ask authors/readers for more resources
Aims: The SLC47A1 gene encodes the multi-drug and toxic excretion-1(MATE1) protein, which plays a key role in the transport and excretion of metformin. This study is to clarify the influence of variants in SLC47A1 (rs2289669 G -> A) on metformin pharmacokinetics and the long-term glucose-lowering effect of metformin. Methods: A total of 220 newly diagnosed type 2 diabetes patients were recruited, genotyped and divided into three groups by SLC47A1 genotypes (G/G, G/A, A/A). Ten patients in each group were randomly selected for metformin pharmacokinetics. All the participants received metformin oral treatment and were followed for one year. Results: After one-year follow-up, the decline of HbA1c level was significantly greater in subjects with variant genotype (AA) than other two groups (-2.32% [-25.4 mmol/mol] in AA vs. -1.16% [-12.7 mmol/mol] in GA, -1.07% [-11.7 mmol/mol] in GG, P < 0.05). Then taking GG genotype as the referent, the association between AA genotype and change of HbA1c still existed after adjusted for age, sex, BMI, baseline HbA1c and diabetes duration (P < 0.05). Pharmacokinetic parameters of metformin indicated that patients carrying MATE1 homozygous A had higher area under the plasma concentration versus time curve (AUC12h), but lower renal clearance (CLR) and renal clearance by secretion (CLSR) than other patients (all P < 0.01). Multivariate lineal stepwise analysis further revealed that SLC47A1 genotype was an independent impact factor for urine excretion of metformin (P < 0.01). Conclusions: SLC47A1 rs2289669 G > A variants improve the glucose-lowering effect of metformin through slowing its excretion in type 2 diabetes populations. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available