Localization of the human multiple drug resistance gene, MDR1, to 7q21.1

Callen, David F.; Baker, Elizabeth; Simmers, R N; Seshadri, Ram; Roninson, Igor B.

doi:10.1007/bf00272381

Cited by 158 publications

(67 citation statements)

References 18 publications

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“…13) Since mdr1a-/-knock-out mice are immunologically normal, the development of spontaneous colitis is presumably due to a defect in the barrier function of the intestinal epithelium. They also indicated that infection with Helicobacter bilis induced diarrhea, weight loss, and IBDs in mdr1a-/-knockout mice.14-16) Macroscopic, microscopic and biochemical examinations have confirmed that the colitis which develops in this model is similar to that of human IBDs, [14][15][16][17] and very recently, it has been confirmed that MDR1 mRNA expression in colonic tissues is down-regulated in patients with UC, but not with CD.18) Next, MDR1 is located on chromosome 7 at q21.1, 19) which was one of the loci of susceptibility toIBDs identified by a genome-wide analysis in an UK cohort, 6) and the linkage in this region has recently been confirmed by genome scan meta-analysis. 20) Finally, in 2003Finally, in -2005, independent groups in Germany and Scotland indicated that a silent genetic polymorphism in exon 26, C3435T, is associated with susceptibility to UC, but not to CD, 21,22) though the results are disputed.…”

mentioning

confidence: 79%

“…18) Next, MDR1 is located on chromosome 7 at q21.1, 19) which was one of the loci of susceptibility to…”

mentioning

confidence: 99%

“…[14][15][16] Macroscopic, microscopic and biochemical examinations have confirmed that the colitis which develops in this model is similar to that of human IBDs, [14][15][16][17] and very recently, it has been confirmed that MDR1 mRNA expression in colonic tissues is down-regulated in patients with UC, but not with CD. 18) Next, MDR1 is located on chromosome 7 at q21.1, 19) which was one of the loci of susceptibility to…”

mentioning

confidence: 99%

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MDR1 C3435T Polymorphism Is Predictive of Later Onset of Ulcerative Colitis in Japanese

Osuga

Sakaeda

Nakamura

et al. 2006

Biological & Pharmaceutical Bulletin

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Inflammatory bowel diseases (IBDs), i.e., Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, impairing quality of life. [1][2][3][4][5] Although the etiology of IBDs still remains unclear, nationwide epidemiologic studies have clarified that the geographic incidence varies substantially, with higher rates in Northern and Western Europe, and Northern America than in Central and Southern Europe and many developing countries.2-5) Epidemiologic and linkage studies strongly suggested the importance of a genetic factor for susceptibility to IBDs, but a genome-wide screening has identified a number of candidate loci, indicating the complexity of IBDs.6) Among candidates, recent attention has focused on the gene MDR1/ABCB1 and its product, multidrug resistant transporter MDR1/P-glycoprotein, which is a glycosylated membrane protein of 170 kDa, belonging to the ATP-binding cassette superfamily of membrane transporters, [7][8][9][10][11][12] as a consequence of several non-clinical and clinical investigations as summarized below. In 1998, Panwala et al. reported that mdr1a-/-knock-out mice were susceptible to a spontaneous UC-like intestinal inflammation under specific pathogen-free conditions. 13) Since mdr1a-/-knock-out mice are immunologically normal, the development of spontaneous colitis is presumably due to a defect in the barrier function of the intestinal epithelium. They also indicated that infection with Helicobacter bilis induced diarrhea, weight loss, and IBDs in mdr1a-/-knockout mice.14-16) Macroscopic, microscopic and biochemical examinations have confirmed that the colitis which develops in this model is similar to that of human IBDs, [14][15][16][17] and very recently, it has been confirmed that MDR1 mRNA expression in colonic tissues is down-regulated in patients with UC, but not with CD.18) Next, MDR1 is located on chromosome 7 at q21.1, 19) which was one of the loci of susceptibility toIBDs identified by a genome-wide analysis in an UK cohort, 6) and the linkage in this region has recently been confirmed by genome scan meta-analysis. 20) Finally, in 2003Finally, in -2005, independent groups in Germany and Scotland indicated that a silent genetic polymorphism in exon 26, C3435T, is associated with susceptibility to UC, but not to CD, 21,22) though the results are disputed. [23][24][25][26] In the present study, the MDR1 polymorphisms of T-129C in the promoter region, a silent C1236T in exon 12, G2677A, T in exon 21, resulting in Ala893Thr and Ala893Ser, respectively, and C3435T were examined in 66 Japanese UC patients and 173 healthy subjects, and their value for predicting UC was analyzed independently. The effects of the G2677T/C3435T haplotype proposed by Johne et al. were also evaluated,27) as well as those of the haplotype assigned by 4 polymorphisms. Here, the patients were stratified into 2 subpopulations based on age at onset; early onset patients and later onset patients, since epidemiologic investigatio...

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mentioning

confidence: 79%

“…18) Next, MDR1 is located on chromosome 7 at q21.1, 19) which was one of the loci of susceptibility to…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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MDR1 C3435T Polymorphism Is Predictive of Later Onset of Ulcerative Colitis in Japanese

Osuga

Sakaeda

Nakamura

et al. 2006

Biological & Pharmaceutical Bulletin

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“…The close physical proximity of the gene locus indicates that ABC-C could be this candidate. Linkage of gene loci for members of the ABC transporter family can also be observed for the human CFTR and MDR1 proteins, which have been mapped to chromosome 7 at bands q31 and q21, respectively [16,17]. In situ hybridization using the murine ABC1 and ABC2 cDNAs as probes on human chromosome spreads identified the ABC1 and ABC2 genes on chromosome 9 region q22-q31 and q34, respectively [12].…”

Section: Database Search and Chromosomal Mappingmentioning

confidence: 96%

Primary structure of a novel ABC transporter with a chromosomal localization on the band encoding the multidrug resistance‐associated protein

Klugbauer¹,

Hofmann²

1996

FEBS Letters

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Complementary DNA clones encoding a novel protein, ABC-C, with the typical structural features of the ABC transporter family were identified in a human medullary thyroid carcinoma cell line. The transporter consists of 1704 amino acid residues with two homologous repeats, each harboring six putative transmembrane helices and an ATPbinding cassette motif. The mRNA is expressed highest in normal lung, but also in varying amounts in other tissues and in C-cell carcinoma. The ABC-C gene is mapped on chromosome 16p13.3, in close physical proximity to another ABC transporter, the multidrug resistance-associated protein. This related protein is assumed to confer resistance to chemotherapeutic drugs in small cell lung carcinoma. The genomic clustering of both transporters, typical also for other members of the ABC family, supports the notion that ABC-C may be involved in development of resistance to xenobiotics.

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“…Also called ABCB1, the MDR1 gene is located in chromosome 7q21.1 (5) and comprises a promoter region of 29 exons, with a total of 209kb (3,6) . MDR1 codes for the P-glycoprotein (PgP) 1, a member of the superfamily of ABC transporters (ATP-binding cassette), which includes proteins that transport a wide variety of substrates (8,9) .…”

Section: Frequency Of the Mdr1 Gene Polymorphism Rs1045642 (C3435t) Imentioning

confidence: 99%

Frequency of the Mdr1 Gene Polymorphism Rs1045642 (C3435t) in HCV-Hiv Co-Infected Patients

Marasca

Machado

Filho

et al. 2016

Arq. Gastroenterol.

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-Background -Due to the high prevalence of co-infection by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) and the severity of these infections, the understanding of the biological mechanisms involved in these processes, including viral behavior and host genetic profile, is of great importance for patient treatment and for public health policies. Some single nucleotide polymorphisms (SNPs) in the human genome, such as the SNP rs1045642 (C3435T) in the MDR1 gene, have been reported to be associated to the sustained virological response (SVR) to HCV treatment in HCV-HIV co-infected patients. Objective -The present study analyzes the MDR1 gene C3435T polymorphism in HCV-HIV co-infected patients.Methods -A total of 99 HCV-HIV patients were included in the study. The DNA was extracted from blood samples, and the SNP rs1045642 was assessed by Real Time PCR (qPCR). Risk factors for acquiring the virus and the SVR after HCV treatment with pegylated interferon-alpha and ribavirin were also analyzed. Results -Among the patients, 54 (54.5%) were male and 45 (45.5%) were female. The average age was 46.1±9.8 years. The SVR after HCV treatment was 40%. The frequencies of MDR1 genotypes CC, CT and TT were 28.3%, 47.5% and 24.2%, respectively. Allele frequencies were 52% for the C allele and 48% for the T allele. No association was found for SNP rs1045642 (C3435T) regarding response to treatment (P=0.308). Conclusion -In this study, the C3435T polymorphism in the MDR1 gene appears not to be associated with SVR in HCV-HIV co-infected individuals. HEADINGS -Hepacivirus. HIV. Single nucleotide polymorphism. P-glycoprotein. Coinfection. Interferon-alpha. Ribavirin.Declared conflict of interest of all authors: none Disclosure of funding: no funding received Financial support: Marasca GS and Souza ACS hold a fellowship from CAPES (Ministry of Education, Brazil).

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Localization of the human multiple drug resistance gene, MDR1, to 7q21.1

Abstract: Multiple drug resistance has been shown to be associated with amplification/increased expression of a gene designated MDR. The localization of one member of the MDR gene family, MDR1, to the long arm of chromosome 7 by in situ hybridization is reported.

Cited by 158 publications

References 18 publications

MDR1 C3435T Polymorphism Is Predictive of Later Onset of Ulcerative Colitis in Japanese

MDR1 C3435T Polymorphism Is Predictive of Later Onset of Ulcerative Colitis in Japanese

Primary structure of a novel ABC transporter with a chromosomal localization on the band encoding the multidrug resistance‐associated protein

Frequency of the Mdr1 Gene Polymorphism Rs1045642 (C3435t) in HCV-Hiv Co-Infected Patients

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