Allele frequency and genotype distribution of a common variant in the 3´-untranslated region of the SLC22A3 gene in patients with type 2 diabetes: Association with response to metformin.
BACKGROUND
Organic cation transporter 3 (OCT3) is an excellent transporter for metformin, which is used as first-line therapy for type 2 diabetes (T2D). OCT3 genetic variants may influence the clinical response to metformin. This study aimed to determine the genotype and allele frequency of OCT3-564G>A (rs3088442) variant and its role in the glycemic response to metformin in patients with newly diagnosed T2D.


METHODS
Based on the response to metformin, 150 patients were classified into two groups: Sixty-nine responders (decrease in glycated hemoglobin [HbA1c] values by more than 1% from the baseline) and 81 nonresponders (decrease in HbA1c values <1% from the baseline). HbA1c levels were determined by chromatography. The variant OCT3-564G>A was genotyped using polymerase chain reaction - based restriction fragment length polymorphism.


RESULTS
The genotypes frequencies were 51.3% GG, 36% AG, and 12.7% AA. Allele frequency of major allele (G) and minor allele (A) in OCT3-564G>A variant was found to be 0.69 and 0.31, respectively. Fasting glucose, HbA1c, body mass index, and lipid profile in both GG genotypes and GA + AA group decreased significantly after 3 months of metformin therapy compared with baseline (P< 0.05). In both responders and nonresponders, HbA1c and fasting glucose levels were lower in patients with the GA + AA genotype than in those with the GG genotype; however, the differences were not statistically significant (P> 0.05).


CONCLUSIONS
The A allele frequency (which may be a protective allele against coronary heart disease) in the Iranian diabetic patients was lower than Iranian, Caucasian and Japanese healthy populations. Metformin is useful in improving the lipid profile, in addition to its impacts in glycemic control, and these effects are regardless of OCT3-564G>A variant.
Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Maryam
M
Ghaffari-Cherati
Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Abdolkarim
A
Mahrooz
Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Mohammad Bagher
MB
Hashemi-Soteh
Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Seyyedeh Raheleh
SR
Hosseyni-Talei
Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Ahad
A
Alizadeh
Medical Diagnostic Laboratory, Bu-Ali Hospital, Mazandaran University of Medical Sciences, Sari, Iran.
Saeid Mofid
SM
Nakhaei
Genetic variation; glycated hemoglobin; metformin; organic cation transporter 3; type 2 diabetes