Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population

Saito, Susumu; Iida, Aritoshi; Sekine, Akihiro; Miura, Yohei; Ogawa, Chie; Kawauchi, Saori; Higuchi, Sadaharu; Nakamura, Yusuke

doi:10.1007/s10038-002-8653-6

Cited by 78 publications

(44 citation statements)

References 23 publications

(34 reference statements)

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“…These findings indicate that mutations in Abcb10 may modify these hematopoietic diseases since the Abcb10 homozygous deletion showed wide effects on function in the heme biosynthesis cascade and erythroblast differentiation. However, there have been no reports showing abnormalities in ABCB10 in human SA and EPP (28,29). This discrepancy between our finding and the results of human genetic analysis can be explained by the complex combination of genetic abnormalities and/or the difficulty of genetic and epidemiologic analysis of SA because of its rarity and the variety of symptoms and severities caused by the disease (30,31).…”

Section: Abcb10contrasting

confidence: 98%

Abcb10 Role in Heme Biosynthesis In Vivo: Abcb10 Knockout in Mice Causes Anemia with Protoporphyrin IX and Iron Accumulation

Yamamoto

Arimura

Fukushige

et al. 2014

Molecular and Cellular Biology

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Abcb10, member 10 of the ABC transporter family, is reportedly a part of a complex in the mitochondrial inner membrane with mitoferrin-1 (Slc25a37) and ferrochelatase (Fech) and is responsible for heme biosynthesis in utero. However, it is unclear whether loss of Abcb10 causes pathological changes in adult mice. Here, we show that Abcb10 ؊/؊ mice lack heme biosynthesis and erythropoiesis abilities and die in midgestation. Moreover, we generated Abcb10 F/؊ ; Mx1-Cre mice, with Abcb10 in hematopoietic cells deleted, which showed accumulation of protoporphyrin IX and maturation arrest in reticulocytes. Electron microscopy images of Abcb10 ؊/؊ hematopoietic cells showed a marked increase of iron deposits at the mitochondria. These results suggest a critical role for Abcb10 in heme biosynthesis and provide new insights into the pathogenesis of erythropoietic protoporphyria and sideroblastic anemia.

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Section: Abcb10contrasting

confidence: 98%

Abcb10 Role in Heme Biosynthesis In Vivo: Abcb10 Knockout in Mice Causes Anemia with Protoporphyrin IX and Iron Accumulation

Yamamoto

Arimura

Fukushige

et al. 2014

Molecular and Cellular Biology

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“…Sequencing of the core promoter region in another European population was reported to identify only SNP e1/-129TϾC where the minor C-allele only occurs at a frequency of 5.9% (Hoffmeyer et al, 2000). In the Japanese population, various groups using either sequencing or single strand conformation polymorphism also identified SNPs i1/ -41(A/G), e1/-129(T/C), and sometimes SNPe1/-145(C/G) at the MDR1 promoter region Tanabe et al, 2001;Saito et al, 2002;Taniguchi et al, 2003;Takane et al, 2004). The minor allele frequency of these SNPs in the Japanese population was reported to be Յ10% (Table 2; Lee et al, 2004a).…”

Section: Discussionmentioning

confidence: 99%

The Promoter Region of theMDR1Gene Is Largely Invariant, but Different Single Nucleotide Polymorphism Haplotypes Affect MDR1 Promoter Activity Differently in Different Cell Lines

Wang

Ngoi²,

Wang³

et al. 2006

Mol Pharmacol

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The MDR1 multidrug transporter represents one of the better characterized drug transporters that play an important role in protecting the body against xenobiotic insults. Single nucleotide polymorphisms (SNPs) and SNP haplotypes within this gene have been variously associated with differences in MDR1 expression/function, drug response as well as disease susceptibility. Nonetheless, the effect of polymorphisms at the MDR1 promoter region on its promoter activity remains less characterized. Through the examination of ϳ1.5 kilobases of MDR1 promoter region from five populations, including the Chinese, Malays, Indians, European Americans, and African Americans, we identified eight low-frequency SNPs, of which only two were polymorphic in at least four of the five populations examined. The other SNPs are mainly population-specific, the majority of which occur only in the African-American population. Recapitulation of the various combinations of SNP haplotypes in vitro in promoter-reporter assays revealed a few notable trends. The African and European American-specific haplotypes tended to result in enhanced MDR1 promoter activity only in the human embryonic kidney (HEK) 293 cell line. Haplotype GCTAACC, which occurs at variable frequencies in all the populations examined, with Asians having much lower frequencies (Ͻ2%) compared with the European Americans/African Americans (Ͼ4%), affected MDR1 promoter activity differently in different cell lines. Compared with the commonest haplotype, GCTA-ACC haplotype resulted in a significant decrease in MDR1 promoter activity in HeLa cells (P Ͻ 0.05) but a significant increase in the same promoter activity in HEK293 cells (P Ͻ 0.05). These results suggest that the MDR1 promoter region is largely invariant but that different haplotypes have differential effects on the MDR1 promoter activity in different cell lines.

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“…The first genetic polymorphism of MDR1 to be identified was a G2677T variant isolated from human adrenal, liver, and kidney samples that results in an Ala893Ser change in Pglycoprotein (19,20 (21)(22)(23)(24)(25)(26)(27)(28). Table I gives a summary of 19 segregating sites, resulting in 20 coding region variants identified in a population of 247 healthy individuals of different ethnic backgrounds (22).…”

Section: Genetic Variation In Mdr1mentioning

confidence: 99%

Functional Implications of Genetic Polymorphisms in the Multidrug Resistance Gene MDR1 (ABCB1)

2004

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The multidrug resistance (MDR1) gene product P-glycoprotein is a membrane protein that functions as an ATP-dependent efflux pump, transporting exogenous and endogenous substrates from the inside of cells to the outside. Physiological expression of P-glycoprotein in tissues with excretory or protective function is a major determinant of drug disposition and provides a cellular defense mechanism against potentially harmful compounds. Therefore, P-glycoprotein has significant impact on therapeutic efficacy and toxicity as it plays a key role in absorption of oral medications from the intestinal tract, excretion into bile and urine, and distribution into protected tissues such as the brain and testes. There is increasing interest in the possible role of genetic variation in MDR1 in drug therapy. Numerous genetic polymorphisms in MDR1 have been described, some of which have been shown to determine Pglycoprotein expression levels and substrate transport. Furthermore, some of these polymorphisms have an impact on pharmacokinetic and pharmacodynamic profiles of drug substrates and directly influence outcome and prognosis of certain diseases. This review will focus on the impact of genetic variation in MDR1 on expression and function of P-glycoprotein and the implications of this variation for drug therapy and disease risk.

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Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population

Cited by 78 publications

References 23 publications

Abcb10 Role in Heme Biosynthesis In Vivo: Abcb10 Knockout in Mice Causes Anemia with Protoporphyrin IX and Iron Accumulation

Abcb10 Role in Heme Biosynthesis In Vivo: Abcb10 Knockout in Mice Causes Anemia with Protoporphyrin IX and Iron Accumulation

The Promoter Region of theMDR1Gene Is Largely Invariant, but Different Single Nucleotide Polymorphism Haplotypes Affect MDR1 Promoter Activity Differently in Different Cell Lines

Functional Implications of Genetic Polymorphisms in the Multidrug Resistance Gene MDR1 (ABCB1)

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