A Cohort Study on Response of T2DM Patients to Oral Antidiabetics and their Association with CYP2C9*3 Gene Polymorphism (rs1057910) in Khyber Pakhtunkhwa, Pakistan
A Cohort Study on Response of T2DM Patients to Oral Antidiabetics and their Association with CYP2C9*3 Gene Polymorphism (rs1057910) in Khyber Pakhtunkhwa, Pakistan
Iram Alam Sthanadar1*, Muhammad Zahid1, Sami Siraj2 and Omar Malik2
ABSTRACT
Type 2 diabetes mellitus (T2DM) is an important public health problem all over the world, affecting approximately 417 million adults which is expected to reach to 592 million by the year 2035 globally. Metformin, sulfonylureas (SFUs) are widely used oral anti-diabetic drugs metabolized by cytochrome P450 belonging to family 2 subfamily C member 9 (CYP2C9). CYP2C9 has shown better glycemic control and reduced the treatment failure rates compared to metformin and its combination therapy. To study the association of CY2PC9 gene variant rs1057910 in T2DM patients of Khyber Pakhtunkhwa (KP) origin, the cohort study was conducted for a period of 12 months including 150 patients receiving metformin, glimepiride and its combination therapy. Purposive sample technique was used for sample collection. Data collection was done by proper questionnaire. DNA was extracted from 200 μL of whole blood samples obtained from the patients by using the Wiz-Prep DNA extraction kit (Wiz-Prep no. W54100). Sanger sequencing was used for genetic analysis. Data analysis was done by using IBMS-KMU SPSS 23 version. The Hardy-Weinberg equilibrium for T2DM subjects was determined using an online HWE calculator. The rs1057910 polymorphism in CY2PC9 gene responsible for drug metabolism was analyzed which showed that our population has high frequency of major allele CC which confirmed that patients receiving metformin, glimepiride and its combination therapy were effective for glycemic control through-out in a 12 months cohort with a p value of <0.0001. The SNP rs1057910 in CYP2C9 was inconsistent with H.W equilibrium and shows disequilibrium in our population. The study found a modest but non-significant effect of the CYP2C9*3 rs1057910 polymorphism on susceptibility to type 2 diabetes in KP Pakistan, highlighting the need for further research on gene-environment and gene-gene interactions.
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