shlokn/autogkb huggingface dataset:
Article: CYP3A5 Gene Variation Influences both Systemic and Intrarenal Tacrolimus Disposition
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*7
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *1/*1 + *1/*7 is associated with increased clearance of tacrolimus in healthy individuals as compared to CYP3A5 *7/*7.
Notes: Healthy individuals with the CYP3A5 *1/*1 or *1/*7 (rs41303343) genotype had 1.6-fold higher oral tacrolimus clearance and 2.0 - 2.7-fold higher metabolite/parent area under the curve (AUC) ratios for 31-desmethyl tacrolimus (31-DMT), 12-hydroxytacrolimus, and 13-desmethyl tacrolimus (13-DMT), as compared to individuals with the *7/*7 genotype. Subjects who carry two copies of loss-of-function CYP3A5 alleles (CYP3A5*3/rs776746, CYP3A5*6/rs10264272 or CYP3A5*7) were pooled together as CYP3A5 non-expressors for this analysis. CYP3A5 *1 allele carriers were pooled togethers as CYP3A5 expressors.
Article: Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2, CYP2C9*3
Drug(s): phenytoin
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2C9 *1/*3 + *2/*3 are not associated with dose of phenytoin in children with as compared to CYP2C9 *1/*1 + *1/*2.
Article: SLCO1B1 genetic variation and hormone therapy in menopausal women
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): conjugated estrogens
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with decreased concentrations of conjugated estrogens in women with Menopause as compared to genotypes CC + CT.
Article: Association between the rs7583431 single nucleotide polymorphism close to the activating transcription factor 2 gene and the analgesic effect of fentanyl in the cold pain test
Gene: ATF2
Variant/haplotype: rs1982235
Drug(s): fentanyl
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to fentanyl in people with Pain, Postoperative as compared to allele T.
Article: VKORC1 and Novel CYP2C9 Variation Predict Warfarin Response in Alaska Native and American Indian People
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele T is not associated with dose of warfarin as compared to allele C.
Notes: in Alaska Native and American Indian People.
Article: IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti–IL-4 receptor α antagonist
Gene: IL4R
Variant/haplotype: rs8832
Drug(s): pitrakinra
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with increased response to pitrakinra in people with Asthma as compared to genotypes AA + AG.
Notes: Subjects with the GG genotype have a reduced frequency of asthma exacerbations and nocturnal awakenings compared to those with the AA + AG genotypes. There is a significant dose-response relationship for both of these phenotypes in subjects with the GG genotype.
Article: Plasma Letrozole Concentrations in Postmenopausal Women With Breast Cancer Are Associated With CYP2A6 Genetic Variants, Body Mass Index, and Age
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*2, CYP2A6*4, CYP2A6*9, CYP2A6*12, CYP2A6*17, CYP2A6*20, CYP2A6*23, CYP2A6*35
Drug(s): letrozole
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 *1/*17 + *20/*23 + *9/*9 + *1/*4 + *1/*2 + *17/*17 + *17/*35 + *2/*9 + *9/*12 + *1/*9 + *1/*12 are associated with decreased clearance of letrozole in women with Breast Neoplasms as compared to CYP2A6 *1/*1.
Notes: Patients were grouped into normal (n = 200; *1/*1), intermediate (IM) (n = 40; *1/*9 and *1/*12), and slow (n = 21; *1/26, *1/35, *20/*23, *9/*9, *1/*4E, *1/*2, *17/*17, *1/*17, *17/*35, *2/*9, *9/*12) metabolizer groups. P-value given here is for slow or intermediate metabolizers compared normal metabolizers [stat_test: kruskal-wallis post hoc test]. CYP2A6*1/*26 and CYP2A6*1/*35 genotypes was consistent with normal metabolizers of letrozole rather than slow metabolizers. CYP2A6*12 was associated more with slow metabolizers than with intermediate metabolizers. CYP2A6*1/*26 and CYP2A6*1/*35(n = 1 each) were excluded from the analysis and CYP2A6*1/*12 (n = 11) were analyzed on the assumption that they related to slow metabolizers, which strengthened the analysis. Please note that this paper originally identified the *4E allele, which has been reassigned to *4 by PharmVar.
Article: CYP3A5 Gene Variation Influences both Systemic and Intrarenal Tacrolimus Disposition
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT is associated with increased metabolism of tacrolimus in healthy individuals as compared to genotype CC.
Notes: Patients who carried the T allele (CYP3A5 *1) had increased renal metabolism of tacrolimus and lower apparent urinary tacrolimus clearance as compared to CC (*3/*3) homozygotes. Decreased accumulation of tacrolimus in the tubular epithelium in carriers of the *1 allele as compared to *3/*3 homozygotes may contribute to interindividual differences in tacrolimus-induced nephrotoxicity. Subjects who carried two copies of a loss-of-function CYP3A5 allele (CYP3A5 *3, *6/rs10264272, *7/rs41303343) were pooled together as CYP3A5 non-expressers for the analysis; CYP3A5 *1 allele carriers were pooled together as CYP3A5 expressers.
Article: Polymorphisms in methotrexate transporters and their relationship to plasma methotrexate levels, toxicity of high-dose methotrexate, and outcome of pediatric acute lymphoblastic leukemia
Gene: SLC19A1
Variant/haplotype: rs1131596
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes AG + GG are not associated with concentrations of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype AA.
Notes: There is no association between selected SNPs and methotrexate plasma level at 48 h between the first dose of methotrexate infusion. med. MTX concentration: AG+GG 0.41 (0.09–34.05)) vs. AA (0.6 (0.14–41.63)). Please note: alleles have been complemented to the + chromosomal strand.
Article: Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes
Gene: CYP2A6
Variant/haplotype: rs28399454
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Allele T is associated with decreased metabolism of nicotine as compared to allele C.
Notes: Assigned as decreased function following in vitro assessments, in vivo associations and variant construct functional assignments. Please note that alleles have been complemented to the positive strand. This is the defining allele of the CYP2A6*17 allele.
Article: Genetic Variation of the Mu Opioid Receptor (OPRM1) and Dopamine D2 Receptor (DRD2) is Related to Smoking Differences in Patients with Schizophrenia but not Bipolar Disorder
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): nicotine
Phenotype category: Other
Significant: no
Association: Genotypes AG + GG are not associated with exposure to nicotine in people with Bipolar Disorder as compared to genotype AA.
Notes: Subgroup analysis of bipolar disorder patients only found no significant difference in number of cigarettes smoked per day between genotype groups.
Article: The pharmacokinetic and pharmacodynamic interaction of clopidogrel and cilostazol in relation to CYP2C19 and CYP3A5 genotypes
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): clopidogrel
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A5 *1/*3 (assigned as intermediate metabolizer phenotype) is not associated with metabolism of clopidogrel in healthy individuals as compared to CYP3A5 *3/*3 (assigned as poor metabolizer phenotype) .
Notes: either when clopidogrel is administered alone or in combination with cilostazole. The authors observed no differences in AUC (ng*hr/ml) or Cmax (ng/ml) values of clopidogrel thiol metabolite when comparing between  CYP3A5 genotype groups. The differences in concentrations of clopidogrel thiol metabolite AUC, or Cmax between the CYP3A5 *1/*3 and CYP3A5 *3/*3 was not significant either when clopidogrel was administered alone or in combiation with cilostazole.
Article: IL28B SNP rs8099917 Is Strongly Associated with Pegylated Interferon-α and Ribavirin Therapy Treatment Failure in HCV/HIV-1 Coinfected Patients
Gene: IFNL3
Variant/haplotype: rs8099917
Drug(s): peginterferon alfa-2a, peginterferon alfa-2b, ribavirin
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with increased response to peginterferon alfa-2a, peginterferon alfa-2b and ribavirin in Hepatitis C, Chronic as compared to genotypes GG + GT.
Notes: The type of peginterferon alfa was not specified.  The patients were co-infected with HIV-1.  An association with SVR (sustained viral response) at 24 weeks was found in HCV genotype 1-infected patients, but not in genotype 3-infected patients.
Article: Breast milk pharmacokinetics of efavirenz and breastfed infants’ exposure in genetically-defined subgroups of mother-infant pairs: an observational study
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes GT + TT are associated with increased concentrations of efavirenz in people with HIV Infections as compared to genotype GG.
Notes: CYP2B6 516G>T was independently associated with efavirenz concentrations in maternal plasma, breast milk, and infant plasma.
Article: Therapeutic efficacy of generic artemether–lumefantrine in the treatment of uncomplicated malaria in Ghana: assessing anti-malarial efficacy amidst pharmacogenetic variations
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3, CYP3A5*6, CYP3A5*7
Drug(s): artemether, dihydroartemisinin
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A5 *1/*3 + *1/*6 + *1/*7 is not associated with decreased concentrations of artemether or dihydroartemisinin in people with Malaria, Falciparum as compared to CYP3A5 *1/*1.
Notes: "Fig 3. Plasma drug concentration of artemether and dihydroartemisinin and CYP2B6 and CYP3A5 expressors. C There were no observed significant differences. D There were no observed significant differences"
Article: SLCO1B1 Phenotype and CYP3A5 Polymorphism Significantly Affect Atorvastatin Bioavailability
Gene: SLCO1B1
Variant/haplotype: SLCO1B1*1, SLCO1B1*5
Drug(s): atorvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: SLCO1B1 *1/*5 + *5/*5 are associated with increased concentrations of atorvastatin in healthy individuals as compared to SLCO1B1 *1/*1.
Notes: Carriers of the SLCO1B1 decreased function (DF) and poor function (PF) phenotypes (*1/*5 and *5/*5) were related to higher AUC/DW, Cmax/DW and to lower Vd/F and Cl/F compared to carriers of the normal function (NF) phenotype (*1/*1).
Article: A Prospective, Randomized Pilot Trial of Model-Based Warfarin Dose Initiation using CYP2C9 Genotype and Clinical Data
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: CYP2C9 *2 is associated with decreased dose of warfarin as compared to CYP2C9 *1.
Notes: This was a pilot study to compare traditional and PGx-guided dosing.
Article: Targeted pharmacogenetic analysis of antipsychotic response in the CATIE study
Gene: KCNMA1
Variant/haplotype: rs35793
Drug(s): quetiapine
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with response to quetiapine in people with Schizophrenia.
Notes: as measured by changes in PANSS-T (positive and negative syndrome scale total score), using a mixed model repeated measures approach. Examined 6789 SNPs - p-value of p< or equal to 5x10-4 was considered significant. Please note: reported allele was C, this has been complemented to the plus chromosomal strand. It was unclear whether the allele was associated with an increased or decreased response to drug.
Article: Polymorphic Variants of SCN1A and EPHX1 Influence Plasma Carbamazepine Concentration, Metabolism and Pharmacoresistance in a Population of Kosovar Albanian Epileptic Patients
Gene: EPHX1
Variant/haplotype: rs2234922
Drug(s): carbamazepine
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype GG is not associated with dose of carbamazepine in people with Epilepsy as compared to genotype AA.
Notes: There was no association between dose (mean daily, or mean maintenance) with the genotype.
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: OPCML
Variant/haplotype: rs751655
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with increased response to methylphenidate in people with Attention Deficit Disorder with Hyperactivity.
Notes: The authors carried out a GWAS in a Spanish cohort of pediatric patients, than performed a meta-analysis using data from the Spanish cohort and data from a Brazilian adult patient cohort.; This variant was not significant in the meta-analysis after Bonferroni correction had been applied, and was nominally significant (i.e did not reach genome-wide significance) in the initial GWAS in the Spanish cohort.; Response was measured on the Clinical Global Impression-Improvement scale (CGI-I). A CGI-I score of two points or less after eight weeks of treatment was considered a good response.
Article: ADH single nucleotide polymorphism associations with alcohol metabolism in vivo
Gene: ADH1C
Variant/haplotype: rs283411
Drug(s): ethanol
Phenotype category: Toxicity, Metabolism/PK
Significant: yes
Association: Allele A is associated with metabolism of ethanol.
Notes: The authors did not report p-value correction for multiple hypotheses (103 snps tested).  Though they report multiple snps are significantly associated with alcohol metabolism (early or late) tested on blood or breath alcohol concentrations, this snp is NOT significant after Bonferroni correction (<0.00049).  Also, the authors did not state which alleles are associated with increased or decreased metabolism.  Instead, they simply report an association with the snp in general.  Note that this gene is on the minus strand.
Article: The ability of plasma cotinine to predict nicotine and carcinogen exposure is altered by differences in CYP2A6: the influence of genetics, race and sex
Gene: CYP2A6
Variant/haplotype: CYP2A6 low activity
Drug(s): cotinine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 low activity is associated with increased metabolism of cotinine in people with Tobacco Use Disorder as compared to CYP2A6 high activity.
Notes: In people with slower relative to faster CYP2A6 activity, cotinine accumulates resulting in substantial differences in cotinine levels for a given tobacco exposure.  Reduced metabolizers were defined as subjects with one or two copies of *2,*4, *7,*9,*10,*12,*17,*35.
Article: The MAOA rs979605 Genetic Polymorphism Is Differentially Associated with Clinical Improvement Following Antidepressant Treatment between Male and Female Depressed Patients
Gene: MAOB
Variant/haplotype: rs1799836
Drug(s): 5-hydroxyindole-3-acetic acid, serotonin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with increased concentrations of 5-hydroxyindole-3-acetic acid and serotonin in women with Depressive Disorder, Major as compared to genotype CC.
Notes: "TT/T females/males had a significantly higher 5HIAA/5HT ratio (2.79 ± 0.27) compared to CC/C females/males (2.18 ± 0.28) following Bonferroni correction"
Article: UGT1A1 Genotype-Dependent Dose Adjustment of Belinostat in Patients With Advanced Cancers Using Population Pharmacokinetic Modeling and Simulation
Gene: UGT1A1
Variant/haplotype: UGT1A1*1, UGT1A1*28, UGT1A1*60
Drug(s): belinostat
Phenotype category: Dosage
Significant: not stated
Association: UGT1A1 *28/*28 + *1/*60 + *60/*60 are associated with decreased dose of belinostat in people with Neoplasms as compared to UGT1A1 *1/*1 + *1/*28.
Notes: Simulated doses of 600 or 400 mg/m2/24h were given to patients with the *1/*1 + *1/*28 and *28/*28 + *1/*60 + *60/*60 genotypes, respectively, in order to provide equivalent belinostat AUCs.
Article: Influence of COMT (rs4680) and DRD2 (rs1076560, rs1800497) Gene Polymorphisms on Safety and Efficacy of Methylphenidate Treatment in Children with Fetal Alcohol Spectrum Disorders
Gene: DRD2
Variant/haplotype: rs1076560
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with increased response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity and Fetal Alcohol Syndrome as compared to allele C.
Notes: "No association of the studied polymorphisms: DRD2 rs1076560:C > A or DRD2 rs1800497:G > A with the efficacy or safety of MPH treatment was observed"
Article: Combinatorial Pharmacogenetic Interactions of Bucindolol and β1, α2C Adrenergic Receptor Polymorphisms
Gene: ADRA2C
Variant/haplotype: rs61767072
Drug(s): bucindolol
Phenotype category: Efficacy
Significant: yes
Association: Genotype GGGGCGGGGCCG/GGGGCGGGGCCG is associated with increased response to bucindolol in people with Heart Failure as compared to genotypes GGGGCGGGGCCG/del + del/del.
Notes: This study was interested in the effect of this SNP in tandem with rs1801253. The effect of this SNP was secondary to that of rs1801253 such that variants of this SNP did not affect patient outcome unless the patient was a variant carrier for rs1801253. Patients homozygous for the Arg amino acid at rs1801253 showed significantly less occurrences of all cause mortality, cardiac transplant, or heart failure hospitalizations as compared to other patients. Patients carrying the Gly amino acid at rs1801253 but were homozygous for the wildtype allele at this SNP responded worse than those that were homozygous for wildtype allele at rs1801253, but much better than patients carrying the variant allele at both SNPs. Patients carrying the variant allele at both SNPs and were treated with bucindolol had worse outcomes than those that were given a placebo.
Article: TET2 and CSMD1genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives
Gene: ANKFN1
Variant/haplotype: rs9915451
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: no
Association: Allele G is associated with decreased response to hydrochlorothiazide in people with Essential hypertension as compared to allele A.
Notes: The SNP was discovered in two independent cohorts, although no SNPs reached genome wide significance. The authors then considered  P<1 x10^-5 as a threshold for significance (based on the results from a Q-Q plot distribution reference line). Using this revised threshold the authors reported that this SNP was associated with a lower decrease in systolic blood pressure after hydrochlorothiazide treatment.
Article: Implications of OPRM1 and CYP2B6 variants on treatment outcomes in methadone-maintained patients in Ontario: Exploring sex differences
Variant/haplotype: rs73568641
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with increased response to methadone in women with Opioid-Related Disorders as compared to allele T.
Notes: The C allele was associated with reduced odds of continued opioid use in female patients undergoing MMT. However, this was not significant. No association was found in male patients. The significance threshold was set at p<0.017. This SNP is described in the paper as an OPRM1 SNP.
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: rs3743075
Drug(s): nicotine
Phenotype category: Other
Significant: no
Association: Allele T is not associated with exposure to nicotine in men as compared to allele C.
Notes: No significant association between this allele and status as a smoker or non-smoker.
Article: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Gene: ABCC4
Variant/haplotype: rs3742106
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with clearance of tenofovir in people with HIV Infections as compared to allele A.
Notes: Based on available allele frequency data, it is assumed that the paper compares the A and C alleles.
Article: MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis
Gene: MTHFR
Variant/haplotype: rs1801133
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele G.
Notes: alleles complemented to plus chromosomal strand. Response measured by ESR, erythrocyte sedimentation rate; TJC, tender joints counts; SJC, swollen joints counts; DAS28, Disease Activity Score in 28 joints. "DAS28 was decreased after the post-treatment in 677TT and 1298AC, but was not statistically significant."
Article: An Intronic Variant in OPRD1 Predicts Treatment Outcome for Opioid Dependence in African-Americans
Variant/haplotype: rs10753331
Drug(s): buprenorphine
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to buprenorphine in people with Opioid-Related Disorders as compared to allele G.
Notes: Efficacy was determined based on the number of opioid-positive drug screens that each patient had during treatment.
Article: Effect of Genetic Variants on Rosuvastatin Pharmacokinetics in Healthy Volunteers: Involvement of ABCG2, SLCO1B1 and NAT2
Gene: TPMT
Variant/haplotype: TPMT intermediate metabolizer
Drug(s): rosuvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: TPMT intermediate metabolizer is associated with decreased dose-adjusted trough concentrations of rosuvastatin in healthy individuals as compared to TPMT normal metabolizer.
Notes: "For TPMT enzyme, a significant decrease in AUC∞/DW (p = 0.031), AUC72h/DW (p = 0.029, pmv = 0.049, β = −0.267, R2 = 0.302) and Cmax/DW (p = 0.004; pmv = 0.011, β=−0.382, R2 = 0.292) parameters was observed when subjects were intermediate metabolizers (IM) in comparison to normal metabolizers (NM) (Table 3)" Authors reference CPIc and Dutch guidelines but do not specify which variants were measured.
Article: Pharmacogenetic Predictors of Adverse Events and Response to Chemotherapy in Metastatic Colorectal Cancer: Results From North American Gastrointestinal Intergroup Trial N9741
Gene: DPYD
Variant/haplotype: rs1801265
Drug(s): FOLFIRI, FOLFOX, irinotecan, oxaliplatin
Phenotype category: Efficacy
Significant: no
Association: Genotypes AG + GG is not associated with response to FOLFIRI, FOLFOX, irinotecan or oxaliplatin in people with Colorectal Neoplasms as compared to genotype AA.
Notes: Patients were taking either IFL (irinotecan + fluorouracil + leucovorin; n=114), FOLFOX (fluorouracil + oxaliplatin + leucovorin; n=299) or IROX (irinotecan + oxaliplatin; n=107). No significant association was seen between this variant and confirmed response rate, overall survival or time to progression in any of the treatment groups OR all treatment groups considered together. Significance level was set at 0.01.
Article: Analysis of CYP2C19 gene polymorphism and influencing factors of pharmacological response of clopidogrel in patients with cerebral infarction in Zhejiang, China
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2, CYP2C19*3
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: yes
Association: CYP2C19 *1/*2 + *1/*3 + *2/*2 + *2/*3 is associated with increased resistance to clopidogrel in people with Stroke as compared to CYP2C19 *1/*1.
Notes: this was greater for the *2/*2+*2/*3 than *1/*2+*1/*3. Two patients with *17 (one was *2/*17 and other was *3/*17) were excluded from analysis.