2 research outputs found
Impacts of Pharmacokinetic Gene Polymorphisms on Steady‐State Plasma Concentrations of Simvastatin in Thai Population
No full textABSTRACT Simvastatin, an HMG‐CoA reductase inhibitor, is widely used for hypercholesterolemia but may cause myotoxicity linked to its plasma concentration. Pharmacokinetic gene polymorphisms influence inter‐individual variability in simvastatin exposure. This study investigated the effects of pharmacokinetic gene polymorphisms on steady‐state simvastatin plasma levels in Thai patients. Eighty‐nine Thai patients with dyslipidemia or coronary artery disease on simvastatin treatment for at least 2 weeks without dose adjustment were recruited from King Chulalongkorn Memorial Hospital. Simvastatin lactone and acid concentrations were measured 12 h post‐dose using UHPLC–MS/MS. Pharmacokinetic gene polymorphisms, including ABCB1, ABCC2, ABCG2, SLCO1B1, SLCO1B3, CYP3A4, and CYP3A5, were genotyped by MassARRAY System. The results showed that patients with the SLCO1B1 c.521TC+CC genotype had significantly higher simvastatin acid levels than those with c.521TT (0.53 vs. 0.19 ng/mL, p = 0.03). Similarly, the SLCO1B1*1b/*15 genotype was associated with higher simvastatin acid levels than SLCO1B1*1a/*1a (0.58 vs. 0.16 ng/mL, p C, alone or with c.388A>G (SLCO1B1*1b/*15), reduces OATP1B1 function, leading to elevated simvastatin acid levels and increased myotoxicity risk. This study confirms the association of SLCO1B1 rs4149056 (c.521T>C) with higher simvastatin plasma levels in Thai patients. The study highlights the potential role of SLCO1B1 genotyping, particularly rs4149056 (c.521T>C) and rs2306283 (c.388A>G), in guiding statin therapy for Thai patients, which could help optimize treatment and reduce adverse effects such as statin‐induced myotoxicity
Impact of gene polymorphisms involved in the vitamin D metabolic pathway on the susceptibility to and severity of autism spectrum disorder
No full textAbstract This study explores the association between genetic variations in the vitamin D pathway and autism spectrum disorder (ASD) susceptibility and severity in Thai children. A total of 276 participants, including 169 children with ASD and 107 healthy controls, were recruited. Genotyping of vitamin D pathway genes (CYP2R1, CYP27B1, GC, and VDR) was conducted using TaqMan-based real-time PCR, while serum vitamin D levels were measured by chemiluminescence immunoassay. ASD severity was assessed via the Childhood Autism Rating Scale, 2nd Edition. Results reveal that the VDR gene (ApaI) rs7975232 is linked to a reduced ASD risk. In contrast, the GC gene rs7041 (A > C) polymorphism shows a significant association with increased ASD risk and severity, particularly in individuals with both the GC gene polymorphism and vitamin D insufficiency. Additionally, there was a higher prevalence of the GC1s isoform and GC1s-GC1s haplotype in children with ASD, associated with ASD severity. This study identified that individuals possessing GC rs7041 C alleles and the GC1s genotype (rs7041C/rs4588G) exhibit an increased susceptibility to and more severity of ASD. Further studies with larger cohorts are essential to fully understand these genetic polymorphisms’ roles
