Impact of slc47a1 (Rs2289669 g>a) variant on metformin associated lactic acidosis patients

Objective: To address the important role of SLC47A1 G>A (rs2289669) variants in type 2 diabetic Thai patients. The present study was undertaken to investigate the association between disease severity and incidence of those type 2 diabetic patients harboring this genetic abnormality. Materials and Methods: Between January 2014 and December 2015, all patients diagnosed with metformin associated lactic acidosis [MALA] in Burapha University Hospital were enrolled. Full medical record and treatment outcome were collected. RT-PCR were performed in blood samples to identify the SLC47A1 G>A (rs2289669) variations genotyping. Results: There were 10 patients (age 69.4±12.6 years, duration of diabetes 12.1±3.51 years, metformin dose 2,000±471.4 mg/day). The incidence of AA-alleles in MALA patients was 50%, which was significantly higher than the general type 2 diabetic patients (p<0.0001, 95% CI 3.09 to 8.01). Serum creatinine and anion gap of AA patients were significantly higher than non-AA alleles, (7.79+1.80 vs. 3.80+1.77 mg/dL, p = 0.032), (34.2+4.66 vs. 22.0+8.25 mEq/L, p = 0.045), respectively. Conclusion: The present study has been demonstrated the incidence of homozygous MATE/SLC47 gene polymorphism in MALA patients was higher than general type 2 diabetic patient. MALA patients who carry this genetic mutation have more severe disease than those who do not carry this mutation.