OBJECTIVE: To explore the genetic etiology in four patients with hyperbilirubinemia, and discuss the correlation between clinical characteristics and molecular basis. METHODS: The data of clinical manifestation and auxiliary examinations were collected. Genomic DNA of the four patients was extracted and analyzed by next-generation sequencing using the panel including genes involved in hereditary metabolic liver diseases. Suspected variants were verified by Sanger sequencing. RESULTS: All of the four patients were males with normal liver enzymes. It was revealed that all the patients had heterozygous variants, among which c.3011C>T, c.2443C>T and c.2556del were the variants which have not been reported previously. CONCLUSION All of the patients were diagnosed as Dubin-Johnson syndrome (DJS) caused by ABCC2 gene variants. The novel variants add to the spectrum of genetic variants of the disease. Because of the favorite prognosis, precise diagnosis can greatly reduce the psychological pressure of patients and avoid excessive treatments. At the same time, it could provide pertinent genetic counseling for the families.
DNA ; Female ; Heterozygote ; Humans ; Jaundice, Chronic Idiopathic/genetics* ; Male ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins/genetics* ; Phenotype

OBJECTIVE: To explore the genetic etiology and differential diagnosis for a patient with jaundice. METHODS: Clinical data of the patient and his parents were collected. Genes associated with metabolic liver diseases were subjected to high-throughput sequencing. The pathogenicity of the candidate variants was predicted by using bioinformatics software. RESULTS: High-throughput sequencing revealed that the proband has harbored two variants of the ABCC2 gene (NM_000392) including c.3011C>T (p.T1004I) and c.3541C>T (p.R1181X), which were respectively inherited from his father and mother. Both variants have been previously unreported and predicted to be pathogenic by bioinformatics analysis. CONCLUSION The proband was diagnosed with Dubin-Johnson syndrome due to the compound heterozygous variants of the ABCC2 gene. Genetic testing has enabled accurate differential diagnosis of Dubin-Johnson syndrome in this patient.
Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Jaundice, Chronic Idiopathic/pathology* ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins/genetics* ; Mutation

Urinary calculi are characterized by high incidence and recurrence rate, which is a challenge in urology. The theory of Randall plaque is widely recognized by scholars. The mechanism of Randall plaque formation includes vascular calcification, osteogenic transformation and so on. However, it still lacks a unified theory for the Randall plaque formation. As an important type of non-coding RNA, long non-coding RNA (lncRNA) is closely related to the occurrence and progress of many diseases. The difference in lncRNA expression between the renal papillary tissues of non-calculous patients and the renal papillary tissues of Randall plaque in renal calculous patients suggests that lncRNA may be involved in the formation of Randall plaque. Pseudoxanthoma elasticum is a rare autosomal recessive hereditary disease, caused by a mutation in the ABCC6 gene. Patients with pseudoxanthoma elasticum have a high prevalence of calculi, and plaque formation is observed in the patient's kidney, which may suggest that mutation in the ABCC6 gene might be involved in the formation of Randall plaque.
Humans ; Kidney ; Kidney Calculi ; Multidrug Resistance-Associated Proteins ; Mutation ; Plaque, Atherosclerotic ; Pseudoxanthoma Elasticum ; Vascular Calcification

A function of the kidney is elimination of a variety of xenobiotics ingested and wasted endogenous compounds from the body. Organic anion and cation transport systems play important roles to protect the body from harmful substances. The renal proximal tubule is the primary site of carrier-mediated transport from blood into urine. During the last decade, molecular cloning has identified several families of multispecific organic anion and cation transporters, such as organic anion transporter (OAT), organic cation transporter (OCT), and organic anion-transporting polypeptide (oatp). Additional findings also suggested ATP-dependent organic ion transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein (MRP) as efflux pump. The substrate specificity of these transporters is multispecific. These transporters also play an important role as drug transporters. Studies on their functional properties and localization provide information in renal handling of drugs. This review summarizes the latest knowledge on molecular properties and pharmacological significance of renal organic ion transporters.
Cloning, Molecular ; Humans ; Ion Transport* ; Kidney* ; Multidrug Resistance-Associated Proteins ; P-Glycoprotein ; Substrate Specificity ; Xenobiotics

ABCC1 gene is expressed in various tissues and organs of the human body, and can transport substrates including drugs, heavy metals, toxic substances and organic anions. Previous research on ABCC1 gene has mostly focused on tumor multidrug resistance. Recently, ABCC1 has been proposed as a candidate gene for hereditary hearing impairment, which has attracted much attention. ABCC1-associated deafness may be related to its role in biological barriers. This article has summarized recent progress in the study of the role of ABCC1 in the blood-testis barrier, placental barrier, blood-brain barrier, blood-labyrinth barrier, which may provide insight into its biological functions.
Biological Transport ; Deafness/genetics* ; Female ; Humans ; Male ; Multidrug Resistance-Associated Proteins/genetics* ; Placenta ; Pregnancy

BACKGROUND: Inorganic arsenic trioxide (As2O3) has emerged as a new drug of choice for refractory acute promyelocytic leukemia (APL). But, the curable disease spectrum and the arsenic resistance in association with the expression of multidrug resistance (MDR) proteins are not yet to be established. METHODS: Five de novo APL and 20 refractory acute leukemia cases were selected. Leukemic cells were cultured for 24 hr in media with various As2O3 concentrations. Apoptotic cells or damaged cells were measured by a morphologic examination after Wright stain and flow cytometry using annexin V/propidium iodide (PI) stain. The lowest concentration of As2O3 at which greater than 90% of leukemic cells were damaged morphologically was defined as the morphologic arsenic sensitivity of leukemic cells. MDR protein markers including multidrug resistance associated protein (MRP), lung resistance protein (LRP), P-glycoprotein (PGP) and glutathinoe-S-transferase (GST) were analyzed by flow cytometry. RESULTS: The leukemic cells from de novo APLs (in 3 of 5) were sensitive to arsenic trioxide, compared to refractory acute leukemia (only 1 of 20). Of the five MDR proteins examined, only PGP was expressed more in the arsenic resistant cases (in 8 of 21) than in the sensitive cases (none of 4) (P=.032). CONCLUSIONS: Refractory acute leukemia had a variable arsenic sensitivity, but were more resistant than de novo APL. The arsenic resistance seems to be related to PGP expression.
Arsenic ; Drug Resistance, Multiple ; Flow Cytometry ; Leukemia* ; Leukemia, Promyelocytic, Acute* ; Lung ; Multidrug Resistance-Associated Proteins ; P-Glycoprotein

PURPOSE: The purpose of this study is to evaluate the correlations between the multidrug resistance-associated protein (MRP) and multidrug resistance (MDR1) gene in osteosarcoma, and their prognostic significances by RT-PCR method. MATERIALS AND METHODS: We isolated RNA from 34 fresh deep-frozen primary osteosarcoma tissue specimens and evaluated the expression level of MRP and MDR1 m-RNA using RT-PCR method. GAPDH was used as the housekeeping gene for the experiment. RESULTS: The average MRP/GAPDH m-RNA ratio was 0.550 and the average MDR1/GAPDH m-RNA ratio was 0.419. There were moderate degree of correlations between MRP/GAPDH m-RNA and MDR1/GAPDH m-RNA ratio (p<0.05). There was significant correlations between the chemotherapy response and the MDR1/GAPDH m-RNA ratio (p<0.05), but not with the MRP/GAPDH ratio. Multivariate analysis for the correlation between the MRP and MDR1 gene expression and the chemotherapy response revealed that only the MDR1/GAPDH m-RNA ratio was significantly related to it (p<0.05). CONCLUSION: There was a moderate degree of correlation between the expressions of MRP and MDR1 genes. However, the chemotherapy response showed significant correlations with the expression of MDR1 gene, but not with MRP gene.
Drug Resistance, Multiple* ; Drug Therapy ; Gene Expression* ; Genes, Essential ; Genes, MDR ; Multidrug Resistance-Associated Proteins* ; Multivariate Analysis ; Osteosarcoma* ; RNA

Anthocyanin biosynthesis is one of the thoroughly studied enzymatic pathways in biology, but little is known about the molecular mechanisms of its final stage: the transport of the anthocyanins into the vacuole. A clear picture of the dynamic trafficking of flavonoids is only now beginning to emerge. So far four different models have been proposed to explain the transport of anthocyanins from biosynthetic sites to the central vacuole, and four types of transporters have been found associated with the transport of anthocyanins: glutathione S-transferase, multidrug resistance-associated protein, multidrug and toxic compound extrusion, bilitranslocase-homologue. The functions of these proteins and related genes have also been studied. Although different models have been proposed, cellular and subcellular information is still lacking for reconciliation of different lines of evidence in various anthocyanin sequestration studies. According to the information available, through sequence analysis, gene expression analysis, subcellular positioning and complementation experiments, the function and location of these transporters can be explored, and the anthocyanin transport mechanism can be better understood.
Anthocyanins ; metabolism ; Biological Transport ; Glutathione Transferase ; metabolism ; Membrane Transport Proteins ; metabolism ; Multidrug Resistance-Associated Proteins ; metabolism ; Plants ; metabolism ; Vacuoles ; metabolism

Although MDR was previously thought to be predominantly caused by the expression of the MDR1 gene, it is now increasingly believed to be caused by other mechanism. Recently, over-expression of the multidrug resistance-associated protein (MRP) was suggested a possible mechanism for non-Pgp mediated MDR. Recent studies showed that MRP can confer resistance to a wide spectrum of natural product drug, but the clinical relevance of MRP-mediated MDR in human cancer is poorly understood. p53 is the most widely known tumor suppressor gene. It has been suggested that mutant p53 is related to abnormal proliferation of cell and some what is been related to cellular apoptosis. To determine the clinical significance of MRP and/or p53 expression in colorectal carcinoma, the authors investigated the expression of the MRP and p53 in 81 cases of primary colorectal carcinoma, the relationship between the MRP and/or p53 expression and clinical parameters including 5-yr. survival rate, and the relationship between the expression of MRP and p53. The results were as follows: 1) Of the 81 colorectal carcinomas, 36 (42%) were MRP positive and 28 (34%) were p53 positive. 2) The expression of MRP and/or p53 was not significantly correlated with sex, age, histologic grades, tumor invasion, tumor location, tumor size, lymph node metastasis, TNM stage and survival of patients. In conclusion, these results suggest that expression of MRP and/or p53 is neither related to the known prognostic factors nor a prognostic factor by itself.
Apoptosis ; Colorectal Neoplasms* ; Genes, Tumor Suppressor ; Humans ; Lymph Nodes ; Multidrug Resistance-Associated Proteins ; Neoplasm Metastasis ; Prognosis ; Survival Rate

Breast Neoplasms ; metabolism ; Female ; Humans ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Receptor, Epidermal Growth Factor ; metabolism ; Receptors, Progesterone ; metabolism