rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study

Khaled Naja; Ali Salami; Said El Shamieh; Rajaa Fakhoury

doi:10.3390/jpm10020053

rs622342 in SLC22A1, *CYP2C9**2 and *CYP2C9**3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study

J Pers Med. 2020 Jun 20;10(2):53. doi: 10.3390/jpm10020053.

Authors

Khaled Naja¹, Ali Salami², Said El Shamieh³, Rajaa Fakhoury³

Affiliations

¹ Department of Biological Sciences, Faculty of Science, Beirut Arab University, Beirut P.O. Box 11-5020, Lebanon.
² Rammal Hassan Rammal Research Laboratory, Physio-toxicity (PhyTox) Research Group, Faculty of Sciences (V), Lebanese University, Nabatieh P.O. Box 6573/14, Lebanon.
³ Department of Medical Laboratory Technology, Faculty of Health Sciences, Beirut Arab University, Beirut P.O. Box 11-5020, Lebanon.

Abstract

Background and objective: Since the treatment outcome with oral anti-diabetics differs between individuals, the objective of this study is to evaluate the significance of rs622342 in SLC22A1, CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910) with regard to the efficacy of metformin/sulfonylurea combination therapy in individuals with type 2 diabetes mellitus (T2DM).

Methods: Eighty-eight Lebanese individuals with T2DM received metformin/sulfonylurea combination therapy over 3 and 6 months. The clinical and biochemical characteristics were collected. Genotyping of rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 was performed using hybridization probes on real-time polymerase chain reaction (PCR) instrument. Statistical analysis was performed using SPSS 22.0.

Results: The levels of fasting blood sugar (FBS) and glycated hemoglobin (HbA1c) showed a statistically significant reduction over 3 and 6 months of follow-up (p < 0.001). An interaction between rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 (p = 0.035) was found associated with reduced levels of HbA1c levels after 3 and 6 months. A significant difference between the means of HbA1c was observed among the different groups after 3 and 6 months (p = 0.004 and p < 0.001, respectively). The most beneficial group was; AA and AC, *1*3, whereas the individuals that benefited the least were CC, *1*3 at 3 and 6 months. In contrast to HbA1c, no interaction was found between the three polymorphisms to affect FBS (p = 0.581).

Conclusion: The combination of metformin/sulfonylurea therapy led to the maximum glycemic control in individuals with T2DM carrying AA or AC genotypes in SLC22A1 and *1*3 in CYP2C9.

Keywords: OCT1; SLC22A1; single nucleotide polymorphisms; type 2 diabetes mellitus.