The association study between changes in HbA1C with rs2250486 and rs67238751 genetic variants for SLC47A1 in newly diagnosed Iranian patients with type 2 diabetes mellitus: 6 months follow-up study.

OBJECTIVES: One of the most well-known oral medications for the treatment of T2DM is metformin. Variants have been found in studies to be useful in detecting new genes connected to T2DM aetiology and affecting metformin's mechanism of action. In this research, we aimed to study two variations of the SLC47A1 gene; rs2250486 and rs67238751, in T2DM patients who had been taking metformin for the first 6 months after the diagnosis in the Iranian population for the first time.

DESIGN AND METHODS: A total of 200 individuals were recruited for the study. According to their glycosylated haemoglobin (HbA1c) levels, the patients were divided into two groups: responders (HbA1c levels were reduced by at least 1% after 6 months of metformin treatment.) and non-responders. DNA was extracted from whole blood and genotyped by Tetra ARMS PCR. High-performance liquid chromatography (HPLC) was used to measure HbA1c levels at the start of the treatment and again 6 months later.

RESULTS: rs2250486 variant in the dominant model reduces the HbA1C levels after 6 months of metformin treatment. In fact, when compared to the T/C + C/C genotypes, the T/T genotype improves HbA1C levels (p-value = .014). Furthermore, in the allelic model, the T allele improves HbA1C levels in comparison to the C allele (p-value = .008). After 6 months of metformin treatment, serum levels of HbA1C in responders were reduced significantly in both groups (T/T and T/C + C/C), (p-value = <.0001). However, the rs67238751 variant did not reveal a meaningful relationship with lower HbA1C levels in any of the models.

CONCLUSIONS: This study found that the rs2250486 variant could be associated with reducing HbA1C levels while the rs67238751 variant, had no relationship.