shlokn/autogkb huggingface dataset:
Article: Effect of ABCB1 (MDR1) haplotypes derived from G2677T/C3435T on the pharmacokinetics of amlodipine in healthy subjects
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): amlodipine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with decreased clearance of amlodipine in healthy individuals as compared to genotypes AA + AC.
Notes: When analyzed in combination with genotypes from rs1045642. The haplotypes were: 2677CC/3435GG, 2677AC/3435AG, 2677AA/3435AA, where rs2032582 = position 2677 and rs1045642 = position 3435.; Individuals with the 2677CC/3435GG haplotype had increased area under the time-concentration curve from 0 to 144 hours (AUC0-144) and from 0 to infinity (AUC0-infinity) and decreased oral clearance (CL/F) as compared to haplotypes 2677AA/3435AA + 2677AC/3435AG, and increased peak plasma concentration (Cmax) as compared to haplotype 2677AA/3435AA ONLY. Please note alleles have been complemented to the plus chromosomal strand.
Article: The Contribution of Common CYP2A6 Alleles to Variation in Nicotine Metabolism Among European Americans
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*2, CYP2A6*4, CYP2A6*9, CYP2A6*14, CYP2A6*38, CYP2A6*46
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 *1 + *46 + *9 + *14 + *38 are associated with increased metabolism of nicotine as compared to CYP2A6 *2 + *4.
Notes: *2 and *4 are used as examples of 'null' alleles. Please note that this study uses the *1B allele (subsequently reassigned as *46 by PharmVar) as the 'reference allele' and that the *38 allele is described in the paper as '*1D-Y351H'.
Article: Germline Variation in Colorectal Risk Loci Does Not Influence Treatment Effect or Survival in Metastatic Colorectal Cancer
Gene: SMAD7
Variant/haplotype: rs4939827
Drug(s): fluorouracil, irinotecan, oxaliplatin
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to fluorouracil, irinotecan and oxaliplatin in people with Colorectal Neoplasms and Neoplasm Metastasis as compared to allele T.
Notes: SNPs were investigated for their effects on response rate, time to progression and overall survival. After accounting for multiple testing there was no association with any SNPs and outcomes of patients with metastatic colorectal cancer.
Article: Association and cis-mQTL analysis of variants in CHRNA3-A5, CHRNA7, CHRNB2, and CHRNB4 in relation to nicotine dependence in a Chinese Han population
Gene: CHRNA3
Variant/haplotype: rs660652
Drug(s): nicotine
Phenotype category: Other
Significant: no
Association: Allele A is not associated with exposure to nicotine in men as compared to allele G.
Notes: No significant association between this allele and status as a smoker or non-smoker.
Article: Pharmacokinetic-Pharmacodynamic interaction associated with venlafaxine-XR remission in patients with major depressive disorder with history of citalopram / escitalopram treatment failure
Gene: SLC6A4
Variant/haplotype: SLC6A4 HTTLPR long form (L allele), SLC6A4 HTTLPR short form (S allele)
Drug(s): venlafaxine
Phenotype category: Efficacy
Significant: no
Association: SLC6A4 HTTLPR long form (L allele) is not associated with response to venlafaxine in people with Depressive Disorder, Major as compared to SLC6A4 HTTLPR short form (S allele).
Notes: The 5-HTTLPR was not associated with significant differences in remission (QIDS-C16) in patients receiving duloxetine (duloxetine after SSRI failure).
Article: CHRNB2 Promoter Region: Association with subjective effects to nicotine and expression differences
Gene: CHRNB2
Variant/haplotype: rs2072658
Drug(s): nicotine
Phenotype category: Other
Significant: yes
Association: Genotype AG is associated with increased response to nicotine in people with daily smoking as compared to genotype GG.
Notes: Response(sweating, heart pounding and nausea) to the first experimental cigarette was measured using the NEQ(nicotine effects scale).  There were no AA subjects.
Article: Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin
Gene: CYP2C9
Variant/haplotype: rs1799853
Drug(s): phenytoin
Phenotype category: Dosage, Metabolism/PK
Significant: no
Association: Allele T is not associated with increased dose of phenytoin in people with Epilepsy as compared to allele C.
Article: Genetic Polymorphisms of GGH and ABCC2 Are Associated with Methotrexate Intolerance in Patients with Rheumatoid Arthritis
Gene: ABCC2
Variant/haplotype: rs717620
Drug(s): methotrexate
Phenotype category: Toxicity
Significant: yes
Association: Genotypes CT + TT is associated with decreased discontinuation of methotrexate in people with Arthritis, Rheumatoid as compared to genotype CC.
Notes: Patients receiving MTX and bDMARD treatment (combined treatment) at the time of the study were considered “tolerant” to MTX. Patients receiving bDMARD monotherapy at the study visit were asked about the reason for MTX discontinuation. In cases of discontinuation due to adverse events or toxicity (such as nausea; vomiting; dyspepsia; alopecia; oral ulcers; leukopenia; hepatic alterations, defined as alanine aminotransferase levels greater than 1.5 times the upper normal limit; or pulmonary toxicity), these patients were considered “intolerant” to MTX.
Article: Genetic variation in the Catechol-O-Methyltransferase (COMT) gene and morphine requirements in cancer patients with pain
Gene: ARVCF, COMT
Variant/haplotype: rs174699
Drug(s): morphine
Phenotype category: Dosage, Efficacy
Significant: yes
Association: Allele T is associated with decreased dose of morphine in people with Neoplasms as compared to allele C.
Notes: This was for alleviation of pain from cancer.  The association was as part of a haplotype consisting of 11 rsIDs (the other rsIDs are rs2075507,rs7287550, rs5746849, rs737866, rs6269, rs2239393, rs4818, rs4680, rs737866, rs165728).  The haplotype was associated with a dose reduction factor of 0.71 .  Authors state that because the SNPs are linked, a strict Bonferroni correction is too conservative; however, that is what has been done here for p value.  Also noted was that the carriers of haplotype 1 have had the cancer diagnosis longer than have carriers of other haplotypes, and so the true difference in morphine requirements may be even greater than observed here.
Article: The effect of alpha-2A adrenergic receptor (ADRA2A) genetic polymorphisms on the depth of sedation of dexmedetomidine: a genetic observational pilot study
Gene: ADRA2A
Variant/haplotype: rs1800544
Drug(s): dexmedetomidine
Phenotype category: Dosage
Significant: no
Association: Allele C is not associated with dose of dexmedetomidine in men as compared to allele G.
Article: Polymorphisms in the A118G SNP of the OPRM1 gene produce different experiences of opioids: A human laboratory phenotype–genotype assessment
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): hydromorphone
Phenotype category: PD
Significant: yes
Association: Genotypes AG + GG is associated with increased response to hydromorphone in healthy individuals as compared to genotype AA.
Notes: "Participants with AG/GG rated low and moderate doses of hydromorphone as significantly more positive (e.g., Good Effects VAS, coasting, drive, friendly, talkative, stimulation) with fewer negative effects (e.g., itchy skin, nausea, sleepiness), and were also observed as being more talkative and energetic relative to persons with AA."
Article: Influence of CYP2C8*2 on the pharmacokinetics of pioglitazone in healthy African American volunteers
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*2
Drug(s): pioglitazone
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2D6 *1/*2 + *2/*2 are not associated with metabolism of pioglitazone in healthy individuals as compared to CYP2D6 *1/*1.
Notes: CYP2D6 *1A/*2 + *2/*2 is not associated with pioglitazone plasma exposure (area under the plasma concentration-time curve (AUC)0-infinity) and half-life (t1/2 ) in healthy African-American volunteers when exposed to pioglitazone in healthy individuals as compared to CYP2D6 *1A/*1A.
Article: Tell-Tale SNPs: The Role of CYP2B6 in Methadone Fatalities
Gene: CYP2B6
Variant/haplotype: rs8192709
Drug(s): methadone
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with concentrations of methadone as compared to allele C.
Article: CYP3A5, ABCB1 and SLCO1B1 Polymorphisms and Pharmacokinetics and Virologic Outcome of Lopinavir/Ritonavir in HIV-infected Children
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): ritonavir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with exposure to ritonavir in children with HIV Infections as compared to allele T.
Notes: No significant association between this variant and ACU0-12 of ritonavir in patients treated with lopinavir/ritonavir. Variant referred to in the paper as T512C.
Article: CYP3A5, ABCB1 and SLCO1B1 Polymorphisms and Pharmacokinetics and Virologic Outcome of Lopinavir/Ritonavir in HIV-infected Children
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): lopinavir, ritonavir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of lopinavir or ritonavir in children with HIV Infections as compared to allele C.
Notes: No association between this variant and clearance of lopinavir or ritonavir in patients treated with lopinavir/ritonavir. Variant referred to in the paper as G2677T.
Article: ASSOCIATION BETWEEN POLYMORPHIC VARIATION IN VDR AND RXRA AND CIRCULATING LEVELS OF VITAMIN D METABOLITES
Variant/haplotype: rs9409929
Drug(s): vitamin d and analogues
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is associated with increased metabolism of vitamin d and analogues in people with Adenoma as compared to allele G.
Notes: This was described as a trend towards increasing 1,25 (OH)2D levels with each additional copy of the A allele.  p was not significant after correction for multiple testing.
Article: Non-linear fluvoxamine disposition
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor metabolizer
Drug(s): fluvoxamine
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2D6 poor metabolizer is not associated with increased concentrations of fluvoxamine in healthy individuals as compared to CYP2D6 normal metabolizer.
Notes: Subjects are phenotyped with  dextromethorphan. 2Pms and 8EMs. Fluvoxamine dose was steadily increased over 4 weeks."The two CYP2D6 PMs had AUC values in the same range as the EMs."
Article: Influence of ADME genomic variants on tacrolimus/sirolimus blood levels and GVHD after allogeneic hematopoietic cell transplantation
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *3/*3 is associated with increased concentrations of tacrolimus in people with hematopoietic stem cell transplantation as compared to CYP3A5 *1/*1 + *1/*3.
Notes: Patients with the *3/*3 genotype had higher median drug levels of tacrolimus as compared to those with the *1/*1 or *1/*3 genotype. Significant results were also observed for the dose-adjusted concentrations (C/D) of tacrolimus (p=0.01).
Article: Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women
Gene: CYP3A5
Variant/haplotype: rs41303343
Drug(s): lumefantrine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is associated with increased concentrations of lumefantrine in women with Malaria and Pregnancy as compared to allele del.
Notes: Median concentrations of lumefantrine 7 days after beginning treatment with artemether-lumefantrine was significantly higher in carriers of the A allele as compared to non-carriers.
Article: The impact of age and CYP2C9 and VKORC1 variants on stable warfarin dose in the paediatric population
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele C is not associated with dose of warfarin in children as compared to allele T.
Notes: CYP4F2 genotype was not associated with stable warfarin dose.
Article: Genome‐Wide Association Approach Identified Novel Genetic Predictors of Heart Rate Response to β‐Blockers
Gene: OR10P1
Variant/haplotype: rs17117817
Drug(s): atenolol, metoprolol
Phenotype category: PD
Significant: yes
Association: Allele G is associated with decreased response to atenolol or metoprolol in people with Hypertension as compared to allele T.
Notes: as measured by decreased heart rate.
Article: Impact of Single Nucleotide Polymorphisms on Plasma Concentrations of Efavirenz and Lopinavir/ritonavir in Chinese Children Infected with the Human Immunodeficiency Virus
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes GT + TT is associated with increased concentrations of efavirenz in children with HIV Infections as compared to genotype GG.
Article: Potentially Functional SNPs (pfSNPs) as Novel Genomic Predictors of 5-FU Response in Metastatic Colorectal Cancer Patients
Gene: WDR7
Variant/haplotype: rs501415
Drug(s): capecitabine, fluorouracil
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to capecitabine and fluorouracil in people with Neoplasm Metastasis as compared to allele A.
Article: IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti–IL-4 receptor α antagonist
Gene: IL4R
Variant/haplotype: rs2239347
Drug(s): pitrakinra
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with increased response to pitrakinra in people with Asthma as compared to genotypes AC + CC.
Notes: Subjects with the AA genotype have a reduced frequency of asthma exacerbations compared to those with the AC + CC genotypes.
Article: Carfilzomib and lenalidomide response related to VEGF and VEGFR2 germline polymorphisms
Gene: VEGFA
Variant/haplotype: rs833061
Drug(s): carfilzomib, dexamethasone, lenalidomide
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CT + TT is associated with increased response to carfilzomib, dexamethasone and lenalidomide in people with Multiple Myeloma as compared to genotype CC.
Notes: Authors indicate repose as CR/nCR/sCR but do not define these and non-response as VGPR and PR/SD (which assume to mean progression/stable disease). They also test "minimum residual disease negativity" MRD- as measure of response.
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: CYP3A5
Variant/haplotype: rs41303343
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with trough concentration of tacrolimus in people with Kidney Transplantation and Transplantation as compared to allele del.
Notes: This study was attempting to validate reported variants and tacrolimus trough concentration in a large population of African American and European American kidney transplant patients, this was one of the variants that passed validation. Direction of effect was not stated. This variant was only present in the AA population.
Article: Genetic variants in combination with early partial improvement as a clinical utility predictor of treatment outcome in major depressive disorder: the result of two pooled RCTs
Gene: HTR1A
Variant/haplotype: rs6295
Drug(s): milnacipran
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CG are associated with increased response to milnacipran in people with Depressive Disorder as compared to genotype GG.
Notes: depressive symptoms measured on Hamilton Rating Scale for Depression and outcome as change in symptoms, as measured 6 weeks after drug, following 10 days washout.
Article: Disposition of clozapine in man: lack of association with debrisoquine and S-mephenytoin hydroxylation polymorphisms
Gene: CYP2D6
Variant/haplotype: CYP2D6*1
Drug(s): clozapine
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2D6 *1 is not associated with metabolism of clozapine in healthy individuals.
Notes: CYP2D6 genotype does not impact clozapine disposition.
Article: Hypertension Susceptibility Loci and Blood Pressure Response to Antihypertensives – Results from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study
Gene: FGF5
Variant/haplotype: rs1458038
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to hydrochlorothiazide in people with Hypertension as compared to allele T.
Notes: Not significant when using Bonferroni-corrected alpha of 0.0014. Response was assessed by change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after 9 weeks of treatment.
Article: Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate
Gene: ADRA2A
Variant/haplotype: rs1800544
Drug(s): buprenorphine, methadone
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is not associated with response to buprenorphine or methadone in people with Opioid-Related Disorders as compared to genotypes CC + CG.
Notes: Response defined by changes in the rate of dropout from treatment between genotypes.
Article: Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*4
Drug(s): sertraline
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *2 + *3 + *4 are associated with increased concentrations of sertraline as compared to CYP2C19 *1/*1.
Notes: Compared to the reference group (CYP2C19*1/*1), patients homozygous for the non-functional CYP2C19 alleles (*2, *3, or *4) had a 2.3-fold (n = 29, p < 0.001) increase in serum concentrations of sertraline. Patients heterozygous for the non-functional alleles of CYP2C19 in combination with either CYP2C:TG or *1 had 1.21-fold and 1.37-fold increased sertraline concentration, respectively.
Article: CYP2D6 Genetic Variation and Beta-Blocker Maintenance Dose in Patients with Heart Failure
Gene: CYP2D6
Variant/haplotype: CYP2D6*4
Drug(s): metoprolol
Phenotype category: Dosage
Significant: yes
Association: CYP2D6 *4 is associated with decreased dose of metoprolol in people with Heart Failure.
Notes: Patients treated with metoprolol with 7.7 times more likely to have a lower maintenance dose of metoprolol for every *4 allele present.
Article: Effects of NT5C2 germline variants on 6-mecaptopurine metabolism in children with acute lymphoblastic leukemia
Gene: CNNM2
Variant/haplotype: rs58700372
Drug(s): mercaptopurine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CC + CT are associated with decreased metabolism of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT.
Notes: This variant is associated with a significant decrease in TGN metabolite levels during 6-MP treatment in Children With Acute Lymphoblastic Leukemia. The study also showed that rs58700372 directly altered the activity of an intronic enhancer, with the variant allele linked to higher transcription activity and reduced 6-MP metabolism (lower TGN).
Article: VKORC1 and Novel CYP2C9 Variation Predict Warfarin Response in Alaska Native and American Indian People
Gene: CYP4F2
Variant/haplotype: rs2189784
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele G is not associated with dose of warfarin as compared to allele A.
Notes: in Alaska Native and American Indian People.
Article: L‐thyroxine doses required for TSH suppression in patients with differentiated thyroid cancer: Effect of a novel UGT1 marker, rs11563250A > G
Gene: MROH2A, UGT1A
Variant/haplotype: rs11563250
Drug(s): levothyroxine
Phenotype category: Dosage
Significant: no
Association: Allele G is not associated with increased dose of levothyroxine in people with Thyroid Neoplasms.
Article: Novel LZTR1 germline mutation as a mechanism of resistance to osimertinib in EGFR-mutated lung adenocarcinoma: a case report
Gene: LZTR1
Variant/haplotype: rs1411200130
Drug(s): osimertinib
Phenotype category: Efficacy
Significant: no
Association: Allele G is associated with increased resistance to osimertinib in women with Non-Small Cell Lung Carcinoma.
Notes: "Here we present a patient with initial stage IIIA (T1b cN2 M0) adenocarcinoma of the lung, with confirmed EGFR exon 19 mutation (c.2236–2250del) with potential resistance to TKIs due to her leucine-zipper-like transcriptional regulator-1 (LZTR1) c.1653C>G variant. " Mapped by search of ClinVar.
Article: No significant influence of OCT1 genotypes on the pharmacokinetics of morphine in adult surgical patients
Gene: SLC22A1
Variant/haplotype: rs34059508
Drug(s): morphine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with exposure to morphine in people with Pain, Postoperative as compared to allele G.
Notes: Analyzed as part of haplotypes with rs12208357, rs72552763 and rs34130495. There was a non-significant trend for patients carrying reduced function alleles to have increased exposure to morphine, but the change in exposure is not large enough to be of clinical importance.
Article: Intestinal CYP3A4 and Midazolam Disposition in vivo Associate with VDR Polymorphisms and Show Seasonal Variation
Gene: VDR
Variant/haplotype: rs1544410
Drug(s): midazolam
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele C is associated with increased clearance of midazolam as compared to allele T.
Notes: CC > CT > TT.
Article: Neurotrophic Tyrosine Kinase Receptor Type 2 (NTRK2) Gene Associated with Treatment Response to Mood Stabilizers in Patients with Bipolar I Disorder
Gene: NTRK2
Variant/haplotype: rs1387923
Drug(s): lithium
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with response to lithium in people with Bipolar Disorder as compared to genotypes AG + GG.
Article: Association of CYP2C19 Polymorphisms and Lansoprazole-Associated Respiratory Adverse Effects in Children
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*8, CYP2C19*9
Drug(s): lansoprazole
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *2 + *3 + *8 + *9 (assigned as poor metabolizer phenotype) is associated with decreased metabolism of lansoprazole in children with Asthma as compared to CYP2C19 *1/*1 (assigned as normal metabolizer phenotype) .
Notes: CYP2C19 poor metabolizers (defined as having one or more of the following alleles: *2, *3, *8, or *9) were found to have significantly higher mean plasma concentrations of lansoprazole as compared to extensive metabolizers (defined as having two wildtype alleles). Some patients in the cohort included in the analysis also had the *17 allele, but how these were taken into consideration in terms of phenotype was not detailed.
Article: Thiopurine dose intensity and treatment outcome in childhood lymphoblastic leukaemia: the influence of thiopurine methyltransferase pharmacogenetics
Gene: TPMT
Variant/haplotype: TPMT*1, TPMT*2, TPMT*3A, TPMT*3C, TPMT*9, TPMT*21, TPMT*33, TPMT*34
Drug(s): mercaptopurine, thioguanine
Phenotype category: Dosage
Significant: yes
Association: TPMT *1/*2 + *1/*3A + *1/*3C + *1/*9 + *1/*21 + *1/*33 + *1/*34 is associated with decreased dose of mercaptopurine or thioguanine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to TPMT *1/*1.
Notes: As compared to those with the wild-type genotype (*1/*1), those patients heterozygous for the TPMT variant alleles had a 1) a lower average dose (70.4% vs 78.0%, where dose given as the % of standard protocol dose), 2) a greater percentage of time spent at no dose (20.8% vs 15.5%) and 3) a smaller percentage of time where the dose was escalated (2.4% vs 5.8%).