From SNPedia
| Geno
|
Mag
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Summary
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| (A;A)
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0
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normal
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| (A;G)
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|
carrier of one CYP3A4*1B allele
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| (G;G)
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2
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2.5x increased risk for prostate or ovarian cancer; CYP3A4*1B homozygote
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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 [1]]
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]
[PMID 19921206] Association of polymorphisms in CYP19A1 and CYP3A4 genes with lower urinary tract symptoms, prostate volume, uroflow and PSA in a population-based sample
| PharmGKB | PA165111315 |
| Name | CYP3A4*1B, CYP3A4:-392A>G, G allele |
| 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 |
| Gene | CYP3A4, CYP3A |
| Featue | Intron, Intron |
| Evidence | PubMed ID:14515059 |
| Drugs | |
| Diseases | Adenocarcinoma, Carcinoma, Small Cell, Carcinoma, Squamous Cell |
| Curation Level | Curated |
[PMID 20617557] Functional polymorphisms in the CYP3A4, CYP3A5, and CYP21A2 genes in the risk for hypertension in pregnancy
[PMID 20685352] Functional polymorphisms in the CYP3A4, CYP3A5, and CYP21A2 genes in the risk for hypertension in pregnancy
| PharmGKB | PA164857055 |
| Name | CYP3A4*1B |
| 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. |
| Gene | CYP3A4, CYP3A |
| Featue | Intron, Intron |
| Evidence | PubMed ID:19440701 |
| Drugs | indinavir |
| Diseases | HIV Infections |
| Curation Level | Curated |
| PharmGKB | PA164920322 |
| Name | CYP3A4*1B, CYP3A4:-392A>G |
| Annotation | Patients with CYP3A4*1B (vs ref) had greater clearance of docetaxel |
| Gene | CYP3A4, CYP3A |
| Featue | Intron, Intron |
| Evidence | PubMed ID:18509327 |
| Drugs | docetaxel |
| Diseases | |
| Curation Level | Curated |
| PharmGKB | PA165109241 |
| Name | CYP3A4 *1B, CYP3A4:(-290)A>G |
| 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. |
| Gene | CYP3A4, CYP3A |
| Featue | Intron, Intron |
| Evidence | PubMed ID:19376514 |
| Drugs | cyclophosphamide |
| Diseases | Breast Neoplasms, Ovarian Failure, Premature |
| Curation Level | Curated |
| PharmGKB | PA165110779 |
| Name | CYP3A4*1B, CYP3A4:-392A>G, G allele |
| 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 |
| Gene | CYP3A4, CYP3A |
| Featue | Intron, Intron |
| Evidence | PubMed ID:14515059 |
| Drugs | |
| Diseases | Adenocarcinoma, Carcinoma, Small Cell, Carcinoma, Squamous Cell |
| Curation Level | Curated |
| PharmGKB | PA165109628 |
| Name | CYP3A4*1B |
| 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 |
| Gene | CYP3A4, CYP3A |
| Featue | Intron, Intron |
| Evidence | PubMed ID:19127255 |
| Drugs | |
| Diseases | Ovarian Neoplasms |
| Curation Level | Curated |
| PharmGKB | PA165110655 |
| Name | CYP3A4*1B, CYP3A4-V, 5'-flanking region -392A>G, -392 G allele |
| 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. |
| Gene | CYP3A4, CYP3A |
| Featue | Intron, Intron |
| Evidence | PubMed ID:12966368 |
| Drugs | cyclosporine, tacrolimus |
| Diseases | Organ Transplantation, Transplantation |
| Curation Level | Curated |
| PharmGKB | PA165111313 |
| Name | CYP3A4*1B, promoter |
| 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 |
| Gene | CYP3A4, CYP3A |
| Featue | Intron, Intron |
| Evidence | PubMed ID:15122075 |
| Drugs | Tipifarnib |
| Diseases | |
| Curation Level | Curated |
[PMID 21346221] Risk of acute promyelocytic leukemia in multiple sclerosis: Coding variants of DNA repair genes
[PMID 22015057] 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 22120734] Identification of pharmacogenetic predictors of lipid-lowering response to atorvastatin in Chilean subjects with hypercholesterolemia
