A variant 2677A allele of the gene affects fexofenadine disposition

Yi, Sangho; Hong, Kug Sun; Lim, Hyeong‐Seok; Chung, Jae‐Yong; Oh, Dal‐Seok; Kim, Jung-Ryul; Jung, Heechul; Cho, Joo Youn; Yu, Kyung‐Sang; Jang, In‐Jin; Shin, Sang‐Goo

doi:10.1016/j.clpt.2004.08.002

Cited by 106 publications

(63 citation statements)

References 38 publications

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“…Similarly, in Brazilian hypercholesterolemic subjects, the frequency was 0.47 for T allele (Rodrigues et al, 2005). In addition, the frequency found in our study, for the T allele of the variant 3435C> T is similar to that observed in Asian population such as Koreans (0.37) (Yi et al, 2004), higher in Rapanui populations (0.75) (Wielandt et al), and differs significantly from that observed in Afro-Americans (0.21) (Kajinami et al, 2004b), Africans (0.17), European Caucasian (0.52) (Ameyaw et al, 2001) and Oceania population (0.53) (Roberts et al, 2002).…”

Section: Discussionsupporting

confidence: 72%

Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia

et al. 2011

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SUMMARY: Interindividual differences in activity and expression of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P-glycoprotein (P-gp, encoded by ABCB1 gene) contribute considerably to lipid-lowering efficacy of statin treatment in subjects with hypercholesterolemia. Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to result from genetic polymorphisms encoding their genes. However, the available data indicate that the frequencies of ABCB1, CYP3A4 and CYP3A5 gene polymorphisms differ significantly across populations. Thus, the aim of the present study was to determine the allelic frequency of three common variants of these genes in Chilean individuals with primary hypercholesterolemia (HC) and controls. A total of 135 unrelated patients (44 ± 7 years old) with diagnosis of hypercholesterolemia (Total cholesterol ≥ 240 mg/dL) and 120 normolipidemic healthy controls (40 ± 10 years old; total cholesterol ≤ 200 mg/dL) were included in this study. The 3435C>T (MDR1), -290A>G (CYP3A4) and 6986A>G (CYP3A5) gene polymorphisms were analyzed by PCR-RFLP. The genotype distribution for 3435C>T variant of ABCB1 in HC patients (CC: 49%, CT: 37%, TT: 14%) and controls (CC: 41%, CT: 48%, TT: 11%) was comparable (P=0.186). Similarly, the genotype distribution for -290A>G polymorphism of CYP3A4 in HC subjects (AA: 73%, AG: 27%, GG: 0%) and controls (AA: 71%, AG: 29%, GG: 0%) was equivalent (P = 0.863). Finally, the genotype distribution for 6986A>G variant of CYP3A5 in HC individuals (AA: 4%, AG: 41%, GG: 55%) and controls (AA: 4%, AG: 47%, GG: 49%) was similar (P=0.594). The allelic frequencies of 3435C>T (ABCB1), -290A>G (CYP3A4) and 6986A>G (CYP3A5) polymorphisms are similar between Chilean HC patients and controls, and comparable to frequencies found in Asian populations.

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Section: Discussionsupporting

confidence: 72%

Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia

et al. 2011

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“…Most common approach in determination of the influence of gene variation is haplotype assessment because it may provide a better understanding of the observed inconsistences and are promising predictor of the functional consequences of ABCB1 polymorphisms. It has been confirmed that the use of ABCB1 haplotypes is superior in prediction of the pharmacokinetics of digoxin [22], cyclosporine [23] and fexofenadine [24], as well as intestinal expression of ABCB1 mRNA [25]. A correlation was observed between the 1236T, 2677T and 3435T haplotype and decreased irinotecan clearance in Japanese patients with cancer.…”

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confidence: 55%

Genotype Variability and Haplotype Profile of Abcb1 (Mdr1) Gene Polymorphisms in Macedonian Population

Naumovska

Nestorovska

Sterjev

et al. 2014

Prilozi

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The aim of this study was to evaluate the most common ABCB1 (MDR1, P-glycoprotein) polymorphisms in the population of R. Macedonia and compare the allele and haplotype frequencies with the global geographic data reported from different ethnic populations. The total of 107 healthy Macedonian individuals from the general population was included. Genotypes for the ABCB1 for three polymorphisms C1236T [rs1128503], G2677A/T [rs2032582] and C3435T [rs1045642] were analyzed by Real-Time PCR. Obtained allele frequencies for these three SNPs were similar to those observed in other European Caucasians. The detected genotype frequencies were 33.6% for 1236CC, 44.9% for 1236CT and 21.5% for 1236TT in exon 12; 32.7%, 44.9% and 22.4% for 2677GG, 2677GT and 2677GT consecutively in exon 21; and 25.2% for 3435CC, 52.3% for 3435CT and 22.5% for 3435TT in exon 26.Strong LD was observed in our study among all = 0.859, r 2 = 0.711). Eight different haplotypes were identified and the most prominent was the CGC haplotype (45.3%). Our study was the first to have documented the distribution of ABCB1 alleles, genotypes and haplotypes in the population of R. Macedonia. The obtained results can help in the prediction of different response to the drugs that are P-glycoprotein substrates. Additionally, in the era of individualized medicine the determination of the P-glycoprotein genotype might be a good predictive marker for determination of the subpopulations with higher risk to certain diseases.

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“…Drug metabolizing enzymes and membrane transporters of these agents affect their in vivo disposition, and polymorphisms of these genes may influence function and explain some of the inter-individual variability. [1][2][3][4][5][6][7] Commonly used cytotoxics such as docetaxel and doxorubicin have narrow therapeutic indices and significant inter-individual variations in drug disposition. Both drugs are effluxed from cells expressing ABCB1 and metabolized mainly in the liver, with CYP3A being the main metabolizing enzyme of docetaxel.…”

Section: Introductionmentioning

confidence: 99%

PXR, CAR and HNF4α genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients

et al. 2007

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A variant 2677A allele of the gene affects fexofenadine disposition

Cited by 106 publications

References 38 publications

Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia

Frequency of Common Variants in Genes Involved in Lipid-Lowering Response to Statins in Chilean Subjects with Hypercholesterolemia

Genotype Variability and Haplotype Profile of Abcb1 (Mdr1) Gene Polymorphisms in Macedonian Population

PXR, CAR and HNF4α genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients

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