{{Rsnum
|rsid=2740574
|Gene=CYP3A
|Chromosome=7
|position=99784473
|Orientation=minus
|GMAF=0.2011
|Gene_s=CYP3A4
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
}}The [[rs2740574]](G) allele encodes a variant form of [[CYP3A4]] known as CYP3A4*1B. 

[[rs2740574]](G) alleles are associated with an ~10 fold higher risk of aggressive [[prostate cancer]] in African American males. [PMID 16414488, OMIM [http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=124010]]

A pooled study (1,400+ samples) along with a replication study conducted by members of the Ovarian Cancer Association Consortium found a 2.5-2.8x increased risk for [[ovarian cancer]] for [[rs2740574]](G;G) individuals (CI: 1.2-6.5, p=0.017). The authors note that CYP3A4 encodes a key enzyme in estrogen metabolism and which may be linked to ovarian carcinogenesis.{{PMID|19127255|OA=1
}}

{{PMID Auto
|PMID=19921206
|Title=Association of polymorphisms in CYP19A1 and CYP3A4 genes with lower urinary tract symptoms, prostate volume, uroflow and PSA in a population-based sample
|OA=1
}}

{{PharmGKB
|RSID=rs2740574
|Name_s=CYP3A4*1B; CYP3A4:-392A>G, G allele
|Gene_s=CYP3A4, CYP3A
|Feature=Intron, Intron
|Evidence=PubMed ID:14515059
|Annotation=Risk or phenotype-associated allele: CYP3A4*1B, rs2740574 G allele. Phenotype: CYP3A4*1B (rs2740574 G) allele carriers show a significantly increased risk for SCLC (OR = 2.25, p = 0.02), which showed a gender difference comparing the risk for females (OR 3.04, p = 0.06) versus males (OR = 1.00). Heavier smoking male CYP3A4*1B (G) allele carriers (> or = 20 pack-years) showed increased risk of lung cancer (OR = 3.42, p = 0.001) compared to *1A/*1A (rs2740574 GG) carriers with lower tobacco exposure (<20 pack-years). The respective risk was greater in women than for men (OR = 8.00, p = 0.005). Study size: 1562 cancer cases, 432 controls. Study population/ethnicity: A case-control study was conducted in 801 Caucasian lung cancer patients that included 330 adenocarcinomas, 260 squamous cell carcinomas, 171 small cell lung cancers, and 432 Caucasian hospital-based controls. Significance metric(s): OR = 1.00 - 8.00; p = 0.005 - 0.06. Type of association: GN; PK; CO
|Drugs=
|Drug Classes=
|Diseases=Adenocarcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell
|Curation Level=Curated
|PharmGKB Accession ID=PA165111315
}}

{{PMID Auto
|PMID=20617557
|Title=Functional polymorphisms in the CYP3A4, CYP3A5, and CYP21A2 genes in the risk for hypertension in pregnancy
}}
{{PMID Auto
|PMID=20685352
|Title=Functional polymorphisms in the CYP3A4, CYP3A5, and CYP21A2 genes in the risk for hypertension in pregnancy
}}

{{PharmGKB
|RSID=rs2740574
|Name_s=CYP3A4:-392A>G; CYP3A4*1B
|Gene_s=CYP3A4, CYP3A
|Feature=Intron, Intron
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/cyp3a4/variant.jsp
|Annotation=Defining variant for CYP3A4*1B; well studied, conflicting results on effect on gene transcription, no clear consensus on its significance for drug disposition, may be assocated with an increased risk of developing endometrial cancer after tamoxifen treatment.
|Drugs=tamoxifen
|Drug Classes=
|Diseases=Endometrial Neoplasms
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161145181
}}

{{PharmGKB
|RSID=rs2740574
|Name_s=CYP3A4*1B
|Gene_s=CYP3A4, CYP3A
|Feature=Intron, Intron
|Evidence=PubMed ID:19440701
|Annotation=A study of 40 protease inhibitor-naive HIV patients found that the CYP3A4*1B polymorphism influenced the pharmacokinetics of indinavir and, to some extent, the biochemical safety of indinavir.
|Drugs=indinavir
|Drug Classes=
|Diseases=HIV Infections
|Curation Level=Curated
|PharmGKB Accession ID=PA164857055
}}

{{PharmGKB
|RSID=rs2740574
|Name_s=CYP3A4*1B; CYP3A4:-392A>G
|Gene_s=CYP3A4, CYP3A
|Feature=Intron, Intron
|Evidence=PubMed ID:18509327
|Annotation=Patients with CYP3A4*1B (vs ref) had greater clearance of docetaxel
|Drugs=docetaxel
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA164920322
}}

{{PharmGKB
|RSID=rs2740574
|Name_s=CYP3A4 *1B; CYP3A4:(-290)A>G
|Gene_s=CYP3A4, CYP3A
|Feature=Intron, Intron
|Evidence=PubMed ID:19376514
|Annotation=Risk or phenotype-associated allele: G. Phenotype: In a study of breast cancer patients receiving cyclophosphamide based treatment, subjects younger than 45 years old at chemotherapy with CYP3A4*1B variants had significantly longer time to chemotherapy-related ovarian failure than CYP3A4*1A homozygotes. Study size: 127. Study population/ethnicity: Premenopausal women with breast cancer receiving cyclophosphamide. Significance metric(s): HR = 0.25; 95% CI 0.07-0.9; p = 0.3. Type of association: CO.
|Drugs=cyclophosphamide
|Drug Classes=
|Diseases=Breast Neoplasms; Ovarian Failure, Premature
|Curation Level=Curated
|PharmGKB Accession ID=PA165109241
}}

{{PharmGKB
|RSID=rs2740574
|Name_s=CYP3A4*1B; CYP3A4:-392A>G, G allele
|Gene_s=CYP3A4, CYP3A
|Feature=Intron, Intron
|Evidence=PubMed ID:14515059
|Annotation=Risk or phenotype-associated allele: CYP3A4*1B, rs2740574 G allele. Phenotype: CYP3A4*1B (rs2740574 G) allele carriers show a significantly increased risk for SCLC (OR = 2.25, p = 0.02), which showed a gender difference when analyzing females (OR 3.04, p = 0.06) and males (OR = 1.00) separately. Heavier smoking male CYP3A4*1B (G) allele carriers (> or = 20 pack-years) showed increased risk of lung cancer (OR = 3.42, p = 0.001) compared to *1A/*1A (rs2740574 GG) carriers with lower tobacco exposure (<20 pack-years). The respective risk was greater in women than for men (OR = 8.00, p = 0.005). Study size: 1562 cancer cases, 432 controls. Study population/ethnicity: A case-control study was conducted in 801 Caucasian lung cancer patients that included 330 adenocarcinomas, 260 squamous cell carcinomas, 171 small cell lung cancers and 432 Caucasian hospital-based controls. Significance metric(s): OR = 1.00-8.00; p = 0.005-0.06. Type of association: GN; PK
|Drugs=
|Drug Classes=
|Diseases=Adenocarcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell
|Curation Level=Curated
|PharmGKB Accession ID=PA165110779
}}

{{PharmGKB
|RSID=rs2740574
|Name_s=CYP3A4*1B
|Gene_s=CYP3A4, CYP3A
|Feature=Intron, Intron
|Evidence=PubMed ID:19127255
|Annotation=risk allele=G; risk of ovarian cancer= OR is 2.81 among carriers of two copies of the minor allele 95% CI 1.20-6.56, P=0.017; no risk for heterozygous carriers; study size=969 cases and 3491 controls; ethnicity: white, black, latina
|Drugs=
|Drug Classes=
|Diseases=Ovarian Neoplasms
|Curation Level=Curated
|PharmGKB Accession ID=PA165109628
}}

{{PharmGKB
|RSID=rs2740574
|Name_s=CYP3A4*1B, CYP3A4-V, 5'-flanking region -392A>G; -392 G allele
|Gene_s=CYP3A4, CYP3A
|Feature=Intron, Intron
|Evidence=PubMed ID:12966368
|Annotation=Risk or phenotype-associated allele: CYP3A4*1B (rs2740574) G allele. Phenotype: Of 108 renal transplant patients taking cyclosporine (CsA), 94 (87.1%) were carriers of the CYP3A4*1/*1 (rs2740574 AA) wild-type genotype, 9 (8.3%) were heterozygous CYP3A4*1/*1B (rs2740574 AG), and 5 (4.6%) were homozygous CYP3A4*1B (rs2740574 GG). There was no significant genotypic association between the CYP3A4*1B allele and CsA dose requirement (mg/kg), C(0) (ng/ml), or dose-adjusted C(0) (ng/ml per mg/kg) at 3 and 12 months after transplantation. Of 64 patients taking tacrolimus, 7 (10.9%) were heterozygous CYP3A4*1/*1B (rs2740574 AG), and 3 (4.7%) were homozygous CYP3A4*1B (rs2740574 GG). In these 64 patients taking tacrolimus, a trend was observed toward a lower dose-adjusted C(0) for CYP3A4*1B allele carriers (rs2740574 GA or GG), as compared to CYP3A4*1/*1 (rs2740574 AA) genotype carriers (p = 0.01). Comparison between all CYP3A4*1B (rs2740574) G allele carriers (n = 10) and carriers of the CYP3A4*1/*1 (rs2740574 AA) genotype (n = 54) showed a significant difference in tacrolimus dose-adjusted C(0) (p = 0.003), which remained statistically significant at month 12. A significantly higher tacrolimus dose was required in patients carrying the CYP3A4*1B (G) allele compared to CYP3A4*1/*1 (AA) genotype carriers at month 3 (p = 0.01) and at month 12 (p = 0.03). Study size: 108 administered cyclosporine, 64 administered tacrolimus. Study population/ethnicity: Renal transplant recipients from the outpatient clinic of the Erasmus Medical Center in Rotterdam in the Netherlands, who had received a renal graft at least 1 year before the start of the study and were administered CsA (n = 108) or tacroliums (n = 64). Significance metric(s): Not significant for CsA; p = (0.003 - 0.03) for tacrolimus. Type of association: GN; PK.
|Drugs=cyclosporine; tacrolimus
|Drug Classes=
|Diseases=Organ Transplantation; Transplantation
|Curation Level=Curated
|PharmGKB Accession ID=PA165110655
}}

{{PharmGKB
|RSID=rs2740574
|Name_s=CYP3A4*1B, promoter
|Gene_s=CYP3A4, CYP3A
|Feature=Intron, Intron
|Evidence=PubMed ID:15122075
|Annotation=Risk or phenotype-associated allele: none. Phenotype: There was no significant association between systemic exposure of tipifarnib (AUC levels) and CYP3A4*1B genotype. Study size: 28 (16 male). Study population/ethnicity: Caucasian cancer patients, aged 34-75. Significance metric(s): Not significant, p = 0.46. Type of association: GN; PK
|Drugs=Tipifarnib
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165111313
}}

{{PMID Auto
|PMID=21346221
|Title=Risk of acute promyelocytic leukemia in multiple sclerosis: Coding variants of DNA repair genes
}}

{{PMID Auto
|PMID=22015057
|Title=Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study
}}

{{PMID Auto
|PMID=22120734
|Title=Identification of pharmacogenetic predictors of lipid-lowering response to atorvastatin in Chilean subjects with hypercholesterolemia
}}

{{PMID Auto
|PMID=16172230
|Title=Risk of testicular germ cell cancer in relation to variation in maternal and offspring cytochrome p450 genes involved in catechol estrogen metabolism.
}}

{{PMID Auto
|PMID=17615053
|Title=Polymorphisms in the cytochrome P450 genes CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1, CYP19A1 and colorectal cancer risk.
|OA=1
}}

{{PMID Auto
|PMID=18163429
|Title=Genetic polymorphisms in CYP17, CYP3A4, CYP19A1, SRD5A2, IGF-1, and IGFBP-3 and prostate cancer risk in African-American men: the Flint Men's Health Study.
|OA=1
}}

{{PMID Auto
|PMID=18547414
|Title=Genotyping panel for assessing response to cancer chemotherapy.
|OA=1
}}

{{PMID Auto
|PMID=18566991
|Title=Joint effects of inflammation and androgen metabolism on prostate cancer severity.
|OA=1
}}

{{PMID Auto
|PMID=18632753
|Title=Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes.
|OA=1
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{{PMID Auto
|PMID=18936436
|Title=Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.
|OA=1
}}

{{PMID Auto
|PMID=19076156
|Title=Polymorphisms of drug-metabolizing enzymes (GST, CYP2B6 and CYP3A) affect the pharmacokinetics of thiotepa and tepa.
|OA=1
}}

{{PMID Auto
|PMID=19154420
|Title=The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC.
|OA=1
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{{PMID Auto
|PMID=19239339
|Title=Associations between CYP2B6 polymorphisms and pharmacokinetics after a single dose of nevirapine or efavirenz in African americans.
|OA=1
}}

{{PMID Auto
|PMID=19287484
|Title=Clique-finding for heterogeneity and multidimensionality in biomarker epidemiology research: the CHAMBER algorithm.
|OA=1
}}

{{PMID Auto
|PMID=19679043
|Title=African American-preponderant single nucleotide polymorphisms (SNPs) and risk of breast cancer.
|OA=1
}}

{{PMID Auto
|PMID=20021678
|Title=Evaluation of self-reported ethnicity in a case-control population: the stroke prevention in young women study.
|OA=1
}}

{{PMID Auto
|PMID=20170205
|Title=Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part I.
}}

{{PMID Auto
|PMID=20214406
|Title=Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part II.
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{{PMID Auto
|PMID=20354687
|Title=Explaining variability in ciclosporin exposure in adult kidney transplant recipients.
|OA=1
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{{PMID Auto
|PMID=20389299
|Title=Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism.
|OA=1
}}

{{PMID Auto
|PMID=20459744
|Title=Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study.
|OA=1
}}

{{PMID Auto
|PMID=21480817
|Title=Pharmacogenetics of tacrolimus after renal transplantation: analysis of polymorphisms in genes encoding 16 drug metabolizing enzymes.
}}

{{PMID Auto
|PMID=22466345
|Title=Joint effects of smoking and gene variants involved in sex steroid metabolism on hot flashes in late reproductive-age women.
|OA=1
}}

{{GET Evidence
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs2740574
|overall_frequency_n=97
|overall_frequency_d=128
|overall_frequency=0.757812
|n_genomes=45
|n_genomes_annotated=0
|n_haplomes=80
|n_articles=7
|n_articles_annotated=3
|in_pharmgkb=Y
|autoscore=1
|webscore=N
}}

{{PMID Auto
|PMID=23091730
|Title=Androgen Metabolism Gene Polymorphisms, Associations with Prostate Cancer Risk and Pathological Characteristics: A Comparative Analysis between South African and Senegalese Men
|OA=1
}}

{{PMID Auto
|PMID=23146479
|Title=Effect of CYP3A5, CYP3A4, and ABCB1 Genotypes as Determinants of Tacrolimus Dose and Clinical Outcomes After Heart Transplantation
}}

{{PMID Auto
|PMID=23129512
|Title=Polymorphisms in CYP17 and CYP3A4 and prostate cancer in men of African descent
|OA=1
}}

{{PMID Auto
|PMID=23130019
|Title=Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.
|OA=1
}}

{{PMID Auto
|PMID=23175176
|Title=Variation in PAH-related DNA adduct levels among non-smokers: the role of multiple genetic polymorphisms and nucleotide excision repair phenotype.
}}

{{PMID Auto
|PMID=23179402
|Title=CYP3A4*1B polymorphism and cancer risk: a HuGE review and meta-analysis.
}}

{{PMID Auto
|PMID=23501331
|Title=Effects of atorvastatin on CYP3A4 and CYP3A5 mRNA expression in mononuclear cells and CYP3A activity in hypercholeresterolemic patients.
}}

{{PMID Auto
|PMID=24924803
|Title=The PXR rs7643645 Polymorphism Is Associated with the Risk of Higher Prostate-Specific Antigen Levels in Prostate Cancer Patients
}}

{{PMID Auto
|PMID=25217544
|Title=Fatal Methadone Toxicity: Potential Role of CYP3A4 Genetic Polymorphism
}}
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{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}