Impact of ATM and SLC22A1 Polymorphisms on Therapeutic Response to Metformin in Iranian Diabetic Patients

Document Type : Original Article

Authors
Fazlollah Shokri 1
Hamid Ghaedi 1
Soudeh Ghafouri Fard 1
Abolfazl Movafagh 1
Saeid Abediankenari 2
Abdolkarim Mahrooz 3
Zahra Kashi 4
Mir Davood Omrani 1
1 Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Immunogenetic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
3 Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
4 Diabetes Research Center, Imam Teaching Hospital, Mazandaran University of Medical Sciences, Sari, Iran
Abstract
Metabolic syndrome and its pathological sequel, type 2 diabetes are considered as important global health problems. Metformin is the most common drug prescribed for patients with this disorder. Consequently, understanding the genetic pathways involved in pharmacokinetics and pharmacodynamics of this drug can have a considerable effect on the personalized treatment of type 2 diabetes. In this study, we evaluated the association between rs11212617 polymorphism of ATM gene and rs628031 of SLC22A1 gene with response to treatment in newly diagnosed type 2 diabetes patients. We genotyped rs11212617 and rs628031 polymorphism by PCR based restriction fragment length polymorphism (RFLP) and assessed the role of this polymorphisms on response to treatment in 140 patients who have been recently diagnosed with type 2 diabetes and were under monotherapy with metformin for 6 months. Response to metformin was defined by HbA1c and fasting blood sugar (FBS) values. Based on such evaluations, patients were divided into two groups: responders (n= 63) and non- responders (n= 77). No significant association was found between these polymorphisms and response to treatment (OR= 0.86, [95% CI 0.52–1.41], P= 0.32) for rs11212617 and (OR= 0.45, [95% CI 0.64–1.76], P= 0.45) for rs 628031. The reported gene variants in ATM and SLC22A1 are not significantly associated with metformin treatment response in type 2 diabetic patients in an Iranian population.
Keywords
Metformin
type 2 diabetes
pharmacogenetic