shlokn/autogkb huggingface dataset:
Article: Effect of NAT2, GSTM1 and CYP2E1 genetic polymorphisms on plasma concentration of isoniazid and its metabolites in patients with tuberculosis, and the assessment of exposure-response relationships
Gene: CYP2E1
Variant/haplotype: rs6413432
Drug(s): isoniazid
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with increased concentrations of isoniazid in people with Tuberculosis as compared to allele T (assigned as intermediate acetylator phenotype) .
Notes: "Similarly, pharmacokinetic parameters were compared between; patient groups divided according to the presence/absence of the each; CYP2E1 SNPs. Overall, only rs6413432 claimed a statistically significant difference for three INH pharmacokinetic parameters:; INH AUC0–6h, values were significantly higher, while median values; of both AcINH/INH MR and INA/INH MR were significantly lower; in patients with rs6413432 (Table 4)."
Article: Race influences warfarin dose changes associated with genetic factors
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*3
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: CYP2C9 *1/*3 + *3/*3 are associated with decreased dose of warfarin as compared to CYP2C9 *1/*1.
Notes: in both European Americans and African Americans. The dose reduction per variant allele was comparable among European Americans (34.6% vs 34.4%, interaction P value=0.98) vs. African Americans.
Article: Associations between Serotonergic Genes and Escitalopram Treatment Responses in Patients with Depressive Disorder and Acute Coronary Syndrome: The EsDEPACS Study
Gene: SLC6A4
Variant/haplotype: SLC6A4 HTTLPR long form (L allele), SLC6A4 HTTLPR short form (S allele)
Drug(s): escitalopram
Phenotype category: Efficacy
Significant: no
Association: SLC6A4 HTTLPR long form (L allele) is not associated with response to escitalopram 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 (HAMD) in patients receiving escitalopram.
Article: A novel CYP2A6 allele (CYP2A6*35) resulting in an amino acid substitution (Asn438Tyr) is associated with lower CYP2A6 activity in vivo
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*9, CYP2A6*17, CYP2A6*35
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 *1/*35 + *9/*35 + *17/*35 are associated with decreased metabolism of nicotine as compared to CYP2A6 *1/*1.
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: IL10
Variant/haplotype: rs1800896
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with trough concentration of tacrolimus in people with Kidney Transplantation and Transplantation as compared to allele C.
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.
Article: Association of ABCC2 −24C>T Polymorphism with High-Dose Methotrexate Plasma Concentrations and Toxicities in Childhood Acute Lymphoblastic Leukemia
Gene: ABCG2
Variant/haplotype: rs2231137
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with clearance of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele T.
Notes: All patients received four cycles of high dose MTX (5000mg per square meter of body surface area). 1/10th of the dose was administered over 30 minutes (rapid infusion) and the rest was administered continuously over 24hrs. Leucovorin rescue was administered every 6hrs starting 48 hrs after initiation of MTX infusion.
Article: Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity
Gene: DRD2
Variant/haplotype: rs6277
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of methadone in people with Opioid-Related Disorders as compared to allele G.
Notes: Methadone maintenance dose was not associated with genotype of the SNP but it was correlated to the highest dose ever used. Multiple doses versus single dose, body weight, history of cocaine dependence and ethnicity (Asian>Caucasian>African) were independently associated with methadone dose in multiple regression analysis. Please note: alleles have been complemented to the + strand.
Article: Impact of CYP2D6 and CYP2B6 phenotypes on the response to tramadol in patients with acute post‐surgical pain
Gene: CYP2D6
Variant/haplotype: CYP2D6 intermediate metabolizer
Drug(s): o-desmethyltramadol
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 intermediate metabolizer and poor metabolizer is associated with decreased concentrations of o-desmethyltramadol in people with Pain, Postoperative as compared to CYP2D6 normal metabolizer and ultrarapid metabolizer.
Notes: "CYP2D6 IMs+PMs showed significantly lower M130 and M1120 levels than NMs+UMs (univariate p<0.001 and p<0.001; multivariate p<0.001 and p=0.002, unstandardized β coefficient=-13.40, -14.21,  respectively);  the  association  between  M1120  levels  and  CYP2D6 phenotype reached the statistical threshold for significance after the Bonferroni correction for multiple   comparisons  (i.e.,   0.05/3   factors,   i.e.,   sex,   pain   rescue   treatment   and   CYP2D6   phenotype=0.017)."
Article: Comprehensive Assessment of CFTR Modulators’ Therapeutic Efficiency for N1303K Variant
Gene: CFTR
Variant/haplotype: rs80034486
Drug(s): elexacaftor / tezacaftor / ivacaftor
Phenotype category: Efficacy
Significant: not stated
Association: Genotype CG is associated with increased clinical benefit to elexacaftor / tezacaftor / ivacaftor in people with Cystic Fibrosis.
Notes: "In our patient, FEV1 was improved by 4.7% (from 84.1% to 88.8% predicted) after a 3-month treatment.; After 3 months of ETI therapy, the BMI increased by 0.6 kg/m2 (body weight gain was 2.0 kg)." "For the first time, a comprehensive study was conducted on an example of one patient with the N1303K/class I genotype to examine the ETI effect on the restoration of CFTR function using ex vivo (ICM), in vitro (patient’s intestinal organoids) and assessment of clinical parameters before and three months after treatment with ETI. All obtained results are consistent with each other and have proven the effectiveness of ETI for the N1303K variant."
Article: Interaction between ABCG2 421C>A polymorphism and valproate in their effects on steady‐state disposition of lamotrigine in adults with epilepsy
Gene: UGT2B7
Variant/haplotype: rs7668258
Drug(s): lamotrigine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with concentrations of lamotrigine in people with Epilepsy as compared to allele C.
Article: Pharmacogenetics of methylphenidate in childhood attention-deficit/hyperactivity disorder: long-term effects
Gene: ADGRL3
Variant/haplotype: rs1868790
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with decreased response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to genotypes AT + TT.
Notes: For the genetic component, in the CGI-S model, a recessive effects for ADGRL3 rs1868790 was found, which was associated with significant impairment.  Clinical Global Impression-Severity (CGI-S) scale and the Children’s Global Assessment Scale (CGAS). Note the article only states the association of AA in a recessive model without referring to the compared allele. dbSNP references the rsID as T>G and T>A change.
Article: Pharmacokinetics and pharmacogenetics of the MEK1/2 inhibitor, selumetinib, in Asian and Western healthy subjects: a pooled analysis
Gene: CYP2C19
Variant/haplotype: rs12248560
Drug(s): selumetinib
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with metabolism of selumetinib in healthy individuals as compared to allele C.
Notes: Not associated with AUC, AUC0-12 when allele was assessed within ethnic groups (Asian, White, Black) and when all ethnic groups were pooled together. Only P-values for AUC presented here.
Article: Modifying Role of Serotonergic 5-HTTLPR & TPH2 Variants on Disulfiram Treatment of Cocaine Addiction: A Preliminary Study
Gene: SLC6A4
Variant/haplotype: SLC6A4 HTTLPR short form (S allele), SLC6A4 L allele-rs25531C, SLC6A4 L allele-rs25531T
Drug(s): disulfiram
Phenotype category: Efficacy
Significant: yes
Association: SLC6A4 HTTLPR short form (S allele) / HTTLPR short form (S allele) + HTTLPR short form (S allele) / L allele-rs25531C + L allele-rs25531C / L allele-rs25531C (assigned as low activity phenotype) is associated with increased response to disulfiram in people with Cocaine-Related Disorders as compared to SLC6A4 L allele-rs25531T / L allele-rs25531T (assigned as high activity phenotype) .
Notes: There was no difference between disulfiram treatment and placebo for the L allele-rs25531T homozygotes (described in paper as L'L'). Authors grouped L allele-rs25531C with S allele and reported as S' (low serotonin transporter) "During the initial two-week baseline period, the mean rate of cocaine positive urines differed between the S′S′/L′S′ and L′L′ genotype groups (t=2.218, p = 0.0304; 78% versus 92%)"
Article: Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor and ultrarapid metabolizers
Drug(s): (R)-methadone
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2D6 poor metabolizer and ultrarapid metabolizer are not associated with concentrations of (R)-methadone in people with Opioid-Related Disorders as compared to CYP2D6 normal metabolizer.