Dataset Information

The frequency of rs2231142 in ABCG2 among Asian subgroups: implications for personalized rosuvastatin dosing.

ABSTRACT: Statins are widely used medications for the primary and secondary prevention of cardiovascular diseases. Statin-induced musculoskeletal symptoms are the primary adverse drug events contributing to poor adherence to lipid-lowering therapy. Rosuvastatin is characterized by interindividual differences in systemic exposure among different patient population subgroups. The missense variant Q141K within ABCG2, highly prevalent in some Asian subgroups, results in decreased transporter efflux function and increased exposure to rosuvastatin. We aim to highlight the implications of ABCG2 genotype in prescribing rosuvastatin and the ramifications of interpopulation differences in Q141K frequencies in the starting dose of rosuvastatin in major Asian subgroups, using the most recent genetic-based guidelines. The high frequency of Q141K in Filipinos could warrant a lower starting rosuvastatin dose versus non-Filipinos. The Q141K genotype frequencies in Asian subgroups suggest significant interpopulation differences, reinforcing the need to move beyond race-based to genotype-based rosuvastatin dosing.

SUBMITTER: Alrajeh K

PROVIDER: S-EPMC9979151 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The frequency of rs2231142 in ABCG2 among Asian subgroups: implications for personalized rosuvastatin dosing.

Alrajeh Khalifa K Roman Youssef M YM

Pharmacogenomics 20230118 1

Statins are widely used medications for the primary and secondary prevention of cardiovascular diseases. Statin-induced musculoskeletal symptoms are the primary adverse drug events contributing to poor adherence to lipid-lowering therapy. Rosuvastatin is characterized by interindividual differences in systemic exposure among different patient population subgroups. The missense variant Q141K within ABCG2, highly prevalent in some Asian subgroups, results in decreased transporter eff ...[more]

PMID: 36651271

Similar Datasets

Project description:Objectives: Genetic variants and obesity are risk factors for hyperuricemia (HUA). Recent genome-wide association studies have identified ABCG2 rs2231142 as one of the most prominent genetic variants for HUA in an East Asian population. Nevertheless, no large-scale studies have demonstrated any interactive effects between this variant and obesity on serum urate level in Asians. This study aimed to determine the interaction of ABCG2 rs2231142 variant and body mass index (BMI) and its effect on risk of HUA in an East Asian population. Methods: The study was conducted using the Taiwan Biobank database, a population-based biomedical research database of patients with Taiwanese Han Chinese ancestry aged 30-70years between September 2014 and May 2017. Detailed physical information on participants were collected by questionnaires and genotyping using Affymetrix TWB 650K SNP chip. The primary outcome was HUA, defined as a serum uric acid level>7.0mg/dl. Odds ratio (OR) of HUA was analyzed using logistic regression models and the effects of interaction between ABCG2 rs2231142 variants and BMI on serum uric acid level were explored. Results: We identified 25,245 subjects, 4,228 (16.75%) of whom had HUA. The prevalence of HUA was 30% in men and 3.8% in women. The risk of HUA was significantly associated with ABCG2 rs2231142 risk T allele, with more HUA in TT genotype (OR: 2.40, 95% CI: 2.11-2.72, p<0.001) and TG genotype (OR: 1.64, 95% CI: 1.51-1.78, p<0.001) in men, and TT genotype (OR: 2.42, 95% CI: 1.83-3.20, p<0.001) and TG genotype (OR: 1.82, 95% CI: 1.46-2.23, p<0.001) in women, compared with their counterparts. Moreover, we found a strong genetic-environmental interaction associated with the risk of HUA. There was increased risk of HUA by the interaction of ABCG2 rs2231142 variant and BMI for TT genotype (OR: 7.42, 95% CI: 2.54-21.7, p<0.001) and TG genotype (OR: 4.25, 95% CI: 2.13-8.47, p<0.001) in men compared with the GG genotype in men, and for TT genotype (OR: 25.43, 95% CI: 3.75-172.41, p<0.001) and TG genotype (OR: 3.05, 95% CI: 0.79-11.71, p=0.011) in women compared with the GG genotype in women. Conclusion: The risk of HUA was markedly increased by the interaction of ABCG2 rs2231142 variant and BMI, both in men and in women. Body weight control and reduction in BMI are recommended in high-risk patients with the ABCG2 rs2231142 risk T allele.

Project description:AimsThe aim was to comprehensively investigate the effects of genetic variability on the pharmacokinetics of rosuvastatin.MethodsWe conducted a genome-wide association study and candidate gene analyses of single dose rosuvastatin pharmacokinetics in a prospective study (n = 159) and a cohort of previously published studies (n = 88).ResultsIn a genome-wide association meta-analysis of the prospective study and the cohort of previously published studies, the SLCO1B1 c.521 T > C (rs4149056) single nucleotide variation (SNV) associated with increased area under the plasma concentration-time curve (AUC) and peak plasma concentration of rosuvastatin (P = 1.8 × 10-12 and P = 3.2 × 10-15 ). The candidate gene analysis suggested that the ABCG2 c.421C > A (rs2231142) SNV associates with increased rosuvastatin AUC (P = .0079), while the SLCO1B1 c.388A > G (rs2306283) and SLCO2B1 c.1457C > T (rs2306168) SNVs associate with decreased rosuvastatin AUC (P = .0041 and P = .0076). Based on SLCO1B1 genotypes, we stratified the participants into poor, decreased, normal, increased and highly increased organic anion transporting polypeptide (OATP) 1B1 function groups. The OATP1B1 poor function phenotype associated with 2.1-fold (90% confidence interval 1.6-2.8, P = 4.69 × 10-5 ) increased AUC of rosuvastatin, whereas the OATP1B1 highly increased function phenotype associated with a 44% (16-62%; P = .019) decreased rosuvastatin AUC. The ABCG2 c.421A/A genotype associated with 2.2-fold (1.5-3.0; P = 2.6 × 10-4 ) increased AUC of rosuvastatin. The SLCO2B1 c.1457C/T genotype associated with 28% decreased rosuvastatin AUC (11-42%; P = .01).ConclusionThese data suggest roles for SLCO1B1, ABCG2 and SLCO2B1 in rosuvastatin pharmacokinetics. Poor SLCO1B1 or ABCG2 function genotypes may increase the risk of rosuvastatin-induced myotoxicity. Reduced doses of rosuvastatin are advisable for patients with these genotypes.

Dataset Information

The frequency of rs2231142 in ABCG2 among Asian subgroups: implications for personalized rosuvastatin dosing.

Publications

The frequency of rs2231142 in <i>ABCG2</i> among Asian subgroups: implications for personalized rosuvastatin dosing.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets