University of Kerbala
اسم الباحث : مها محمد كاظم مجيد آل طعمة
اسم المشرف : أ.م.مازن حامد عودة ، أ.م.د. حسن محمود موسى
الكلمات المفتاحية :
الكلية : كلية الصيدلة
الاختصاص : الادوية والسموم
سنة نشر البحث : 2020
تحميل الملف : اضغط هنا لتحميل البحث
Summary
Background: Insulin sensitizer’s therapy with metformin is widely used in polycystic ovary syndrome (PCOS) , notwithstanding the treatment effectiveness that shows an individual variations in PCOS patients. Multidrug and toxin extrusion protein (MATE1) has been reported to mediate metformin excretion in kidney and bile. In the current study, the effect of the polymorphisms of MATE1 and the response to metformin has been investigated. There are at least eleven non-synonymous single nucleotide polymorphisms (SNPs) in the MATE1 (SLC47A1) gene, (rs2289669 and rs1961669) SNPs were detected in this study.
Objective: The objective of the study is to determine the clinical, hormonal and biochemical effects for three months of metformin therapy in women with polycystic ovary syndrome and study the effect of MATE1 (SLC47A1) genetic polymorphism on therapeutic response to metformin in polycystic ovary syndrome.
Patients and Methods: This study was an interventional prospective study, 231 women with polycystic ovarian syndrome were selected to participate in this study. All women enrolled in this study with the age range (18-40) years were starting metformin tablet 500 mg per oral twice daily. Blood samples were obtained from eligible patients who had given consent for genetic testing and measurement of follicle stimulating hormone , luteinizing hormone , total testosterone, sex hormone binding globulin, Estradiol, prolactin, thyroid stimulating hormone, fasting insulin, HbA1c%, fasting glucose, and lipid profiles (LDL-C, HDL-C, TG ,Total Cholesterol).
XXII
Results: The results obtained from this study demonstrated that SLC47A1 (G>A) (rs2289669) genetic polymorphism had significant effect on metformin response in patients with polycystic ovary syndrome , while SLC47A1 (A>G) (rs1961669) genetic polymorphisms had no strong effect on metformin response in hormonal and biochemical parameters in the same group of patients. The comparison in demographic and biochemical parameters between pre- and post-metformin treatment results showed improvement in clinical, hormonal and biochemical parameters.
Conclusions: This study revealed that the treatment with metformin showed improvement in menstrual regularity, hormonal and biochemical profile in Iraqi women with polycystic ovarian syndrome. In addition, there was a powerful effect of MATE1 SLC47A1(G>A) (rs2289669) genetic polymorphisms on therapeutic response to metformin in clinical, hormonal and biochemical parameters in those patients, moreover, there was an association between presence of both SNPs in SLC47A1 gene and obesity which considers as most important risk factor for PCOS.
Effect of Genetic Polymorphism of SLC47A1 (MATE1) on the Therapeutic Response of Metformin in Iraqi Women with Polycystic Ovary Syndrome
Summary
Background: Insulin sensitizer’s therapy with metformin is widely used in polycystic ovary syndrome (PCOS) , notwithstanding the treatment effectiveness that shows an individual variations in PCOS patients. Multidrug and toxin extrusion protein (MATE1) has been reported to mediate metformin excretion in kidney and bile. In the current study, the effect of the polymorphisms of MATE1 and the response to metformin has been investigated. There are at least eleven non-synonymous single nucleotide polymorphisms (SNPs) in the MATE1 (SLC47A1) gene, (rs2289669 and rs1961669) SNPs were detected in this study.
Objective: The objective of the study is to determine the clinical, hormonal and biochemical effects for three months of metformin therapy in women with polycystic ovary syndrome and study the effect of MATE1 (SLC47A1) genetic polymorphism on therapeutic response to metformin in polycystic ovary syndrome.
Patients and Methods: This study was an interventional prospective study, 231 women with polycystic ovarian syndrome were selected to participate in this study. All women enrolled in this study with the age range (18-40) years were starting metformin tablet 500 mg per oral twice daily. Blood samples were obtained from eligible patients who had given consent for genetic testing and measurement of follicle stimulating hormone , luteinizing hormone , total testosterone, sex hormone binding globulin, Estradiol, prolactin, thyroid stimulating hormone, fasting insulin, HbA1c%, fasting glucose, and lipid profiles (LDL-C, HDL-C, TG ,Total Cholesterol).
XXII
Results: The results obtained from this study demonstrated that SLC47A1 (G>A) (rs2289669) genetic polymorphism had significant effect on metformin response in patients with polycystic ovary syndrome , while SLC47A1 (A>G) (rs1961669) genetic polymorphisms had no strong effect on metformin response in hormonal and biochemical parameters in the same group of patients. The comparison in demographic and biochemical parameters between pre- and post-metformin treatment results showed improvement in clinical, hormonal and biochemical parameters.
Conclusions: This study revealed that the treatment with metformin showed improvement in menstrual regularity, hormonal and biochemical profile in Iraqi women with polycystic ovarian syndrome. In addition, there was a powerful effect of MATE1 SLC47A1(G>A) (rs2289669) genetic polymorphisms on therapeutic response to metformin in clinical, hormonal and biochemical parameters in those patients, moreover, there was an association between presence of both SNPs in SLC47A1 gene and obesity which considers as most important risk factor for PCOS.
