Sadaf Moeez and Madiha Khalid and Zoya Khalid and Sania Shaheen and Sumbul Khalid
Genotypic and Allelic Distribution of Polymorphic Variants of Gene SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) and Their Association to the Clinical Response to Metformin in Adult Pakistani T2DM Patients
294 - 305
2019
13
6
International Journal of Medical and Health Sciences
https://publications.waset.org/pdf/10010491
https://publications.waset.org/vol/150
World Academy of Science, Engineering and Technology
Background Interindividual variation in response to metformin, which has been considered as a first line therapy for T2DM treatment is considerable. In the current study, it was aimed to investigate the impact of two genetic variants Leu125Phe (rs77474263) and Gly64Asp (rs77630697) in gene SLC47A1 on the clinical efficacy of metformin in T2DM Pakistani patients. Methods The study included 800 T2DM patients (400 metformin responders and 400 metformin nonresponders) along with 400 ethnically matched healthy individuals. The genotypes were determined by allelespecific polymerase chain reaction. Insilico analysis was done to confirm the effect of the two SNPs on the structure of genes. Association was statistically determined using SPSS software. Results Minor allele frequency for rs77474263 and rs77630697 was 0.13 and 0.12. For SLC47A1 rs77474263 the homozygotes of one mutant allele ‘T’ (CT) of rs77474263 variant were fewer in metformin responders than metformin nonresponders (29.2 vs. 35.5 ). Likewise, the efficacy was further reduced (7.2 vs. 4.0 ) in homozygotes of two copies of ‘T’ allele (TT). Remarkably, T2DM cases with two copies of allele ‘C’ (CC) had 2.11 times more probability to respond towards metformin monotherapy. For SLC47A1 rs77630697 the homozygotes of one mutant allele ‘A’ (GA) of rs77630697 variant were fewer in metformin responders than metformin nonresponders (33.5 vs. 43.0 ). Likewise, the efficacy was further reduced (8.5 vs. 4.5) in homozygotes of two copies of ‘A’ allele (AA). Remarkably, T2DM cases with two copies of allele ‘G’ (GG) had 2.41 times more probability to respond towards metformin monotherapy. Insilico analysis revealed that these two variants affect the structure and stability of their corresponding proteins. Conclusion The present data suggest that SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) polymorphisms were associated with the therapeutic response of metformin in T2DM patients of Pakistan.
Open Science Index 150, 2019