Background: Acarbose is an α-glucosidase inhibitor widely used clinically for its significant hypoglycemic effect, albeit with inter-individual variations in response. The sucrase-isomaltase (SI) enzyme is the primary target of acarbose. This study aims to investigate the impact of genetic polymorphisms in the SI gene on the pharmacodynamics of acarbose.
Methods: The Illumina sequencing platform and variation-related databases were employed to analyze probable gene polymorphism sites of SI. Based on the SI polymorphism sites, Chinese subjects (n = 66) were categorized into the wild-type homozygous group (Group A) and the heterozygous variant group (Group B, SI 43 G > T). The validated hexokinase method was utilized to determine glucose concentrations in participants' serum samples. The differences in blood glucose concentration reduction and pharmacodynamic parameters peak concentration (Cmax) and area under the curve (AUC0-2h) after administering the same dose of acarbose were analyzed between the two groups of subjects.
Results: Our results showed that the mean changes in glucose Cmax, AUC0-2h, maximum increase, and maximum decrease in Group B were each lower by 67.66 %, 63.05 %, 53.17 %, and 50 % compared to Group A (all p < 0.05).
Conclusions: These data suggested that genetic polymorphism of the SI gene can significantly influence the hypoglycemic efficacy of acarbose, and the polymorphism of SI is associated with individual differences in clinical treatment outcomes.
Keywords: Acarbose; Blood glucose concentration; Gene polymorphism of drug targets; Pharmacodynamics; Sucrase-isomaltase (SI).
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