Genetics Research
rs3765534
Glutamic Acid 757 → Stop
Gene: ABCC4 — ATP Binding Cassette Subfamily C Member 4 (PEL Blood Group)
Chr 13:95163161
13q32.1
Stop Gained
Population Frequencies12
African
C 0.99654T 0.00346CC 0.993107CT/TC 0.00686TT 0.000033pop=60,058
African American
C 0.99646T 0.00354CC 0.99296CT/TC 0.007005TT 0.000035pop=57,958
African Others
C 0.9986T 0.0014CC 0.997143CT/TC 0.002857TT 0pop=2,100
Asian
C 0.9084T 0.0916CC 0.827864CT/TC 0.161077TT 0.011059pop=16,638
East Asian
C 0.90075T 0.09925CC 0.81371CT/TC 0.174072TT 0.012218pop=12,604
European
C 0.990091T 0.009909CC 0.980312CT/TC 0.019559TT 0.000129pop=495,214
Latin American 1
C 0.9863T 0.0137CC 0.972651CT/TC 0.027349TT 0pop=8,556
Latin American 2
C 0.963T 0.037CC 0.926899CT/TC 0.072207TT 0.000894pop=11,190
Other
C 0.98319T 0.01681CC 0.96663CT/TC 0.033111TT 0.000259pop=30,926
Other Asian
C 0.9323T 0.0677CC 0.872087CT/TC 0.120476TT 0.007437pop=4,034
South Asian
C 0.9558T 0.0442CC 0.914271CT/TC 0.083067TT 0.002662pop=3,756
Studies88
Unread Studies88 ▼
1
Azathioprine (AZA) is an immunosuppressive drug widely used to treat autoimmune diseases but poses a significant risk of myelosuppression. Genetic polymorphisms affecting AZA …
2
… Specifically, the ABCC4 polymorphism rs3765534 is associated with increased thiopurine-induced leukopenia, accompanied by elevated intracellular thioguanine nucleotide levels due …
3
Systemic Lupus Erythematosus (SLE) is an autoimmune disease that often requires treatment with immunosuppressant drugs to manage symptoms and prevent organ damage. …
4
Subacute myelo‐optico‐neuropathy (SMON) is a neurological disorder associated with the administration of clioquinol, particularly at very high doses. Although clioquinol …
5
The role of ABCC4, an ATP-binding cassette transporter, in the process of platelet formation, megakaryopoiesis, is unknown. Here, we show that ABCC4 is highly expressed in …
6
This thesis investigates the intramuscle atorvastatin (ATV) pharmacokinetics contributing to statin-related myotoxicities and non-adherence to cardiovascular disease treatment. The …
7
… performed for ABCC4 rs3765534 (c.2268G>A, p.Glu857Lys) and ABCC11 rs17822931 (c.… However, the ABCC4 rs3765534 and ABCC11 rs17822931 polymorphisms showed no …
8
… in Thai ALL pediatric patients found that the average absolute neutrophil count (ANC) at the 6 th month of the maintenance phase was significantly lower in ABCC4 SNP rs3765534 …
9
6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using …
10
Inherited genetic variation is associated with 6‐mercaptopurine (6‐MP) dose reduction and frequent toxicities induced by 6‐MP. However, the tolerable dose for 6‐MP is not fully …
11
See article in JGH Open, this issue. DOI: https://doi. org/10. 1002/jgh3. 12798. The concept of the four Rs: right drug at the right dose at the right time for the right person is so supremely …
12
血型研究在安全输血, 胎儿和新生儿溶血性疾病, 器官移植等方面具有重要临床意义. 随着下一代 基因组测序技术的迅猛发展, 仅2020 年就有5 个新的红细胞血型系统得到正式命名, 本文主要…
13
薬物治療の治療反応性や有害事象の発現について, 薬物の代謝酵素やトランスポーターの遺伝子 多型との関連性が報告されてきた. 近年では, ゲノムワイド関連解析 (GWAS) によって, 多型と薬物…
14
MRP4 (gene ABCC4) is a polymorphic efflux transporter that has been implicated in drug-induced toxicity. We selected ten commonly observed MRP4 coding variants among …
15
The response to 6-mercaptopurine (6-MP) can be altered by genetic polymorphisms in genes encoding drug-metabolizing enzymes and drug transporters. The purpose of this study …
16
Kawasaki disease (KD) is a systemic vasculitis in childhood, which mainly causes damage to coronary arteries, and intravenous immunoglobulin (IVIG) is the initial therapy…
17
Severe myelosuppression in patients with acute lymphoblastic leukemia (ALL) undergoing 6-MP-based maintenance therapy is attributed to TPMT gene polymorphisms, which …
18
Thiopurines are cornerstone drugs in the treatment of acute lymphoblastic leukaemia (ALL), but their use can be complicated by the incidence of life‐…
19
Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurines (mercaptopurine (MP) and tioguanine (TG)), chemotherapeutic agents used in the treatment …
20
Несмотря на значительные успехи в лечении и высокие показатели излечения острого лимфобластного лейкоза (ОЛЛ) у детей, пациенты все еще страдают от …
21
硫嘌呤类药物是常用的免疫抑制剂, 广泛应用于儿童急性淋巴细胞白血病, 炎症性肠病的治疗, 但 以骨髓抑制, 肝毒性为主的不良反应限制了临床应用. 巯嘌呤的体内代谢转化和处置过程由包括…
22
V proximálních tubulech ledvin a ve střevě jsou lokalizované proteiny (tzv. urátové transportéry), které zajišťují exkreci i reabsorpci kyseliny močové. Polymorfismy v genech kódujících …
23
… Glu757Lys (rs3765534) known to impair the membrane localization of ABCC4 is frequently present in the Japanese population (minor allele frequency, 18%) where it is associated with …
24
… rs3765534 (E757K) is associated with a higher incidence of hematopoietic toxicity caused by thiopurine (an effective immuno-suppressant and anticancer agent) [73, 77]. …
25
Although 90 susceptibility loci of Crohn’s disease (CD) have been confirmed in the Asian population, susceptibility genes for perianal fistula of CD (pCD) in this population …
26
… the WBC count of ITPA 94C > A variant carriers tended to be higher compared to patients without any ITPA 94C > A and multidrug resistance-associated protein (MRP4) (rs3765534) …
27
Clioquinol, one of the first mass-produced drugs, was considered safe and efficacious for many years. It was used as an antifungal and an antiprotozoal drug until it was linked to an …
28
The rationale of the current study was to develop 6-mercaptopurine (6-MP)-mediated hematological toxicity prediction model for acute lymphoblastic leukemia (ALL) …
29
Single Nucleotide Polymorphism at codon 655 of HER2 gene has been extensively evaluated for its role as a susceptible biomarker for breast cancer development and the contradictive …
30
The transport of specific molecules across lipid membranes is an essential function of all living organisms. The processes are usually mediated by specific transporters. One of the …
31
… In our present study, the ABCC4 rs3765534 variant was found … [29], a mutation in ABCC4 rs3765534 dramatically reduces … of patients with the rs3765534 variant were significantly lower …
32
… model of ABCC4 rs3765534 were factors … rs3765534, we assigned each patient to genotype groups according to the variant of NUDT15 activity and dominant model ABCC4 rs3765534 …
33
… ), two SNPs in the ABCC4 gene (rs7986087 and rs868853) that were found to be associated with KD susceptibility in most European populations and another four SNPs (rs3765534, …
34
The thiopurine drugs 6-mercaptopurine (6-MP) and azathiopurine (AZA) are widely used to treat inflammatory bowel disease. However, the incidence of adverse reactions is high, …
35
To find genetic variants that predicted toxicity and/or efficacy of paclitaxel plus carboplatin combination therapy (TC therapy). Patients and methods In a retrospective case-…
36
Genetic polymorphisms contribute to inter-individual variability in the metabolism of multiple clinical drugs, including warfarin, thiopurines, primaquine, and aminoglycosides. A rapid …
37
… ATP-binding cassette subfamily C member 4 (ABCC4), also known as multidrug-resistance protein 4 (MRP4), is associated with thiopurine metabolism; its genetic variant rs3765534 (p.…
38
… The minor allele of ABCC4 SNP 2269G>A (rs3765534, E857K) encodes for a fivefold less expressed variant, resulting in marked MP accumulation and subsequent cytotoxicity in an …
39
SLCO1B1 Polymorphisms are Associated With Drug Intolerance in Childhood Leukemia Maintenance Therapy
Therapy discontinuations and toxicities occur because of significant interindividual variations in 6-mercaptopurine (6-MP) and methotrexate (MTX) response during …
40
SLCO1B1 polymorphisms are associated with drug intolerance in childhood leukemia maintenance therapy
Therapy discontinuations and toxicities occur because of significant interindividual variations in 6-mercaptopurine (6-MP) and methotrexate (MTX) response during …
41
Despite the improved outcome associated with current treatment strategies of pediatric acute lymphoblastic leukemia (ALL), relapse still represents a major challenge. Pediatric ALL …
42
… All patients with both NUDT15 rs116855232 heterozygous variants and ABCC4 rs3765534 variants suffered from severe leukopenia and required 6-MP dose reduction to less than 35 …
43
… MP administration was crosstabulated with variant frequencies, Grade 4 neutropenia (ANC<500/㎕)was significantly more frequent in the carriers of variant T allele in ABCC4 rs3765534…
44
Mercaptopurine (MP) is one of the main chemotherapeutics for acute lymphoblastic leukemia (ALL), and constant MP dose titration is essential to maintain steady drug …
45
… All patients with both NUDT15 rs116855232 heterozygous variants and ABCC4 rs3765534 variants suffered from severe leukopenia and required 6-MP dose reduction to less than 35 …
46
Azathioprine (AZA) is increasingly being prescribed to rheumatoid arthritis (RA) patients. Following oral administration, AZA is converted into its active form. Inflammatory bowel disease (…
47
… Recently, it has been identified a single-nucleotide polymorphism (rs3765534, G2269A) in human ABCC4 gene, which dramatically reduces MRP4 function and results in the …
48
NUDT15 R139C (rs116855232) is a recently identified genetic factor responsible for thiopurine-induced leukocytopenia and hair loss. In this study, we investigated the …
49
小児白血病の治療で使用される薬剤は患者間で薬物動態や薬剤反応性に差があり, 治療変更を 必要とする患者が存在する. 薬物治療への反応性の違いの要因として, 遺伝要因がある. 6-メルカプト…
50
メルカプトプリン (6MP) の副作用である血液毒性の原因として, TPMT の活性低下に加え, 2014 年 に nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) 遺伝子多型が報告された. …
51
T 細胞性急性リンパ性白血病の維持療法中に 6-メルカプトプリン (6-Mp) によると思われる著明な 骨髄抑制を認めた 12 歳男児を経験した. 6-Mp を大幅に減量することにより化学療法を継続すること…
52
… In humans, the minor allele of ABCC4 SNP 2269G>A (rs3765534, E857K) codes for a variant … SNP rs116855232 and ABCC4 SNP rs3765534 occurring at appreciable frequencies in …
53
We investigated the associations between variants in genes coding for enzymes and transporters related to the 6-mercaptopurine pathway and clinical outcomes in pediatric …
54
Multidrug resistance protein 4 (MRP4) is involved in the efflux of nucleoside derivatives and has a role in the determination of drug sensitivity. We investigated the relationship between …
55
Management of the adverse effects of chemotherapy is essential to improve outcome of children with leukemia. Some genetic polymorphisms can predict treatment‐related …
56
Genotyping of TPMT prior to 6‐mercaptopurine (6‐ MP ) administration in acute lymphoblastic leukaemia ( ALL ) patients has been integrated into clinical practice in some populations …
57
Farmakogenomika proučava odnos između genetičkog sklopa individue i njegovog odgovora na lekove i jedan je od stubova personalizovane medicine. Dosadašnji princip lečenja da …
58
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. They are characterized by gain of function mutations in KIT or PDGFRA …
59
研究成果の概要 (和文): 潰瘍性大腸炎・クローン病患者および健常者のサンプル DNA は合計 279 人となり, 3 遺伝子の S NP を TaqMan probe 法と従来の Direct sequence 法の双方で検討を…
60
ATP binding cassette (ABC) transporters are a family of proteins whose activity is vital to cell detoxification, protection against xenobiotics and oxidative stress, and maintenance of …
61
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. This work considers the pharmacological response in GIST patients …
62
Optimisation de la réponse aux thiopurines par la pharmacogénétique: approches in vitro et cliniques
Les thiopurines sont des médicaments cytotoxiques et immunosuppresseurs largement prescrits, notamment dans les maladies inflammatoires chroniques de l’intestin (MICI). Ils …
63
The two basic mainstays of gastrointestinal stromal tumours (GIST) treatment are surgery and imatinib, a selective tyrosine kinase inhibitor that allows achieving a stable or responding …
64
The International Transporter Consortium (ITC) has recently described seven transporters of particular relevance to drug development. Based on the second ITC transporter workshop in …
65
Multilocus genotypes have been shown to be of relevance for using pharmacogenomic principles to individualize drug therapy. As it relates to thiopurine therapy, genetic …
66
… However, it is known that other genetic polymorphisms may be of particular importance for Asian patients, such as SNP rs3765534 in the transporter MRP4, that is polymorphic only in …
67
Understanding the molecular mechanisms and clinical relevance of interindividual variability in drug response remains an important challenge. Pharmacogenomics, the study of genetic …
68
No drug therapy is completely risk free, and the costs associated with non‐response and adverse effects can exceed the cost of the therapy. The ultimate goal of pharmacogenetic …
69
The effect of genetic polymorphisms on the effectiveness of low-dose azathioprine in Japanese patients with systemic lupus erythematosus (SLE) was studied. Methods Sixty-…
70
Drug transport proteins are important determinants of drug absorption, tissue accumulation, and elimination from the body, and there is growing appreciation for the contribution of …
71
… G2269A, rs3765534) caused disrupted membrane localization and reduced MRP4 activity, and it was hypothesized to increase sensitivity to thiopurine-induced myelosuppression as a …
72
炎症性腸疾患の患者数が増加する一方で, さまざまな新しい治療法が導入されている. 患者情報に 基づき個々の患者に最適な治療法を提供する 「個別化医療」 が注目されているが, 炎症性腸疾患…
73
The physiological role of multidrug resistance protein 4 (Mrp4) in the testes is unknown. It was discovered that Mrp4 is expressed primarily in mouse and human Leydig cells; however, …
74
Postpartum haemorrhage (PPH) is the main cause of maternal deaths worldwide. Despite the global effort to improve maternal health, developing countries are still far away from the proposed target of reducing maternal mortality. Therefore, a great deal of research is extensively going on globally to find out and improve appropriate treatment and technologies for low-resourced settings to prevent PPH and the work in this thesis on misoprostol was part of it.
75
… polymorphisms (SNPs), TPMT A719G (rs1142345), inosine triphosphate pyrophosphatase (ITPase) C94A (rs1127354) and multidrug resistance protein 4 MRP4 G2269A (rs3765534), …
76
Clinical validation of genetic polymorphisms and the development of new technologies for the rapid detection of clinically important variants are critical issues in the advancement of …
77
Genetic polymorphisms and mutations in drug metabolizing enzymes, transporters, receptors, and other drug targets (eg, toxicity targets) are linked to inter-individual differences in the …
78
ATP-Binding Cassette (ABC) transporters are important mediators of multidrug resistance (MDR) in patients with cancer. Although their role in MDR has been extensively studied in vitro…
79
In this study, five single nucleotide polymorphisms (SNPs) in the ABCC4, FBN1, CEP152, ZNF804B, and GALNT11 genes were investigated to assess allele frequencies in 14 different …
80
< 目的> ステロイド依存性の炎症性腸疾患 (inflammatoryboweldisease, IBI): 潰瘍性大腸炎, クローン 病) の緩解維持目的において, 2006 年に免疫調節剤 (アザチオプリン (AZA)/6-メルカプトプリン …
81
… For instance, the SNP in MRP4 (rs3765534) was found to dramatically reduce MRP4 function through impairment of membrane localization. 50 This SNP is relatively common in …
82
… This study has even identified an SNP in human MRP4 (rs3765534) that dramatically reduced MRP4 function by impairing its cell membrane localization; this SNP is particularly …
83
… They showed that the MRP4 2269A (E857K, rs3765534) variant dramatically reduces MRP4 functions in mice, and proposed that high frequency of this variant in the Japanese …
84
Individualization of immunosuppressive therapy after solid organ transplantation is a goal that has been pursued for a long time. Nevertheless, in clinical practice, we are still stratifying …
85
Because population stratification can cause spurious associations in case-control studies, understanding the population structure is important. Here, we examined Japanese population …
86
Because population stratification can cause spurious associations in case-control studies, understanding the population structure is important. Here, we examined Japanese population …
87
Thiopurines are effective immunosuppressants and anticancer agents, but intracellular accumulation of their active metabolites (6-thioguanine nucleotides, 6-TGNs) causes dose-limiting hematopoietic toxicity. Thiopurine S-methyltransferase (TPMT) deficiency is known to exacerbate thiopurine toxicity. However, many patients are highly sensitive to thiopurines for unknown reasons. We show that Mrp4 is abundant in myeloid progenitors and tested the role of the multidrug-resistance protein 4 (Mrp4), an ATP binding cassette (ATP) transporter of monophosphorylated nucleosides, in this unexplained thiopurine sensitivity. Mrp4-deficient mice experienced Mrp4 gene dosage–dependent toxicity caused by accumulation of 6-TGNs in their myelopoietic cells. Therefore, Mrp4 protects against thiopurine-induced hematopoietic toxicity by actively exporting thiopurine nucleotides. We then identified a single-nucleotide polymorphism (SNP) in human MRP4 (rs3765534) that dramatically reduces MRP4 function by impairing its cell membrane localization. This SNP is common (>18%) in the Japanese population and indicates that the increased sensitivity of some Japanese patients to thiopurines may reflect the greater frequency of this MRP4 SNP.
88
We studied 111 patients with clinical diagnoses of CBMFSs or associated disorders. Their clinical diagnoses included Fanconi anemia (n= 18), Diamond-Blackfan anemia (n= …
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