Population
/Region
(Type of work/approach) |
Aims |
Drug tested/ Class |
Genes / SNPs / allelic variants studied or identified |
Associated metabolism /disease |
Main findings/conclusions |
Ref. |
80 patients
75 (control group)
Original article
Genotyping |
To screen for the presence of alterations in the phenobarbital-responsive enhancer sequence of the UGT1A1 gene.
To investigate a possible association of these alterations with Gilbert syndrome (GS). |
not applied |
UGT1A1 |
c.-3279T_G |
Gilbert syndrome |
The c.-3279T_G polymorphism was a common finding in both GS and control individuals.
The c.-3279T_G polymorphism of the UGT1A1 gene could be an additional, if only cumulative, risk factor for the development of GS, thus justifying the inclusion of this polymorphism in routine molecular screening protocols. |
[47] |
135 healthy individuals
Original article
Only genotyping |
To characterize 15 genetic polymorphisms in a population sample from Portugal. |
not specified |
CYP2C9 *2
CYP2C9 *3
CYP2C19
CYP3A4*1B
CYP3A5*3C
GSTP1 313A>G
GSTM1*0
ITPA 94 A>C
UGT1A1*28
UGT1A1 - 3156 G>A
ABCB1 1236 C>T
ABCB1 2677 G>A
ABCB1 2677 G>T
ABCG2 421C>A
ERCC2 2251>C
TYMS1 1494del |
Drug metabolism |
Higher frequency of CYP2D6*10, and lower frequency of CYP2D6*6, and duplication of *1 and *2 compared to European population.
The allele frequencies in the Portuguese were very similar to other Europeans. There is evidence of some African influence. |
[8]
|
469 patients /Azores region
Original article
Only Genotyping |
To assess 4 polymorphisms in 3 thrombotic risk genes in 469 healthy blood donors from Azores
To analyze the CYP2C9 (C430T, A1075C) and VKORC1 (G1639A) variants in individuals with predisposition to thrombosis to evaluate their warfarin drug response genetic profiles. |
Antithrombotic Agents |
F5 |
G1691A |
Cardiovascular diseases |
Azores population shows significant differences on allele frequencies of thrombotic risk factors when compared to mainland Portugal.
Thrombotic risk allele frequencies: 1691A (4.9%), 20210A (1.8%), 677T (41.7%) and 1298C (24.8%) were similar to other Caucasians, but significantly different from mainland Portuguese. |
[30] |
Warfarin |
F2 |
G20210 |
|
MTHFR |
C677T
A1298C |
Master’s Thesis |
Two distinct sub-studies were carried out: a descriptive cross-sectional study, whose information was collected from previously defined hospital services; and sub-study 2, which was based on a consensus technique - Delphi Panel. |
|
|
Oncology |
In sub-study 1 information was obtained from 4 oncologic research services, and in these services the use of genetics in therapeutic decisions, when it happens, it is not in a pharmacogenomics perspective, but from a perspective of characterizing the disease or its stage.
In sub-study 2, the institutions identified the indication of the experts, the few responses received were mostly via telephone. Data with potential in cancer prevention and chemotherapy. |
[48] |
45 patients /Centre region
Original article
Only Genotyping |
To analyze the effects of multiple candidate genes on clinical improvement and occurrence of adverse drug reactions, in 45 autistic patients who received monotherapy with risperidone up to 1 year.
Candidate genes involved in the pharmacokinetics and pharmacodynamics of the drug, and the brain-derived neurotrophic factor (BDNF) gene, were analysed. |
Risperidone |
CYP2D6
ABCB1
HTR2A
HTR2C
DRD2
DRD3
HTR6
BDNF |
Autism |
Risperidone therapy is effective in reducing some autism symptoms and caused few serious adverse effects.
The HTR2A c.-1438G4A, DRD3 Ser9Gly, HTR2C c.995G4A and ABCB1 1236C4T polymorphisms were predictors for clinical improvement with risperidone therapy.
The HTR2A c.-1438G4A, HTR2C c.68G4C (p.C33S), HTR6 c.7154–2542C4T and BDNF c.196G4A (p.V66M) polymorphisms influenced prolactin elevation.
HTR2C c.68G4C and CYP2D6 polymorphisms were associated with risperidone-induced increase in BMI or waist circumference.
It was identified several genes implicated in risperidone efficacy and safety in autism patients. |
[31]
|
92 Portuguese
151 Mozambican
91 Colombian subjects
Original article
Only Genotyping
|
To study selected genetic polymorphisms in drug metabolizing enzymes in 3 different ethnic groups - Portugal, Mozambique and Colombia.
PCR-RFLP genotyping methods were developed for drug metabolizing enzymes, namely, cholesterol 7α-hydroxylase, sterol 27-hydroxylase and oxysterol 7α-hydroxylase to characterize the allelic distribution of these polymorphisms among 3 different ethnic/geographic origins. |
not specified |
CYP7A1 |
rs3808607
rs3808608
rs3824260
rs8192874
rs58192875
rs61733615 |
Cardiovascular diseases |
A total of 12 CYP7A1, CYP27A1 and CYP7B1 genetic variants were genotyped.
The variants N233S in CYP7A1 and 1774C>T in CYP7B1 were not detected in any population studied. The promoter polymorphisms in CYP7A1 (−203A>C, −346C>T, −496C>T) had high frequency in the 3 ethnic groups.
G347S (CYP7A1), R164W, A169V and V400A (CYP27A1) were present in a low frequency but with a similar distribution in the 3 groups.
Significant differences were observed for D273N (CYP27A1), −346C>T (CYP7A1), −116C>G and R324H (CYP7B1).
There is a high variability of drug metabolizing enzymes between the populations, indicating that at least some of these polymorphisms are ethnic specific. |
[32]
|
CYP27A1 |
rs59443548
rs11559242
rs6994547 |
CYP7B1 |
rs5935258
rs8192907 |
170 asthmatic individuals and 174 healthy individuals/ Center region
Master’s Thesis
Only Genotyping |
Determine the genotypic and allele frequencies of the repeat polymorphism in intron 4 of eNOS and of nucleotide substitution polymorphisms in amino acid 16 and 27 of ADRẞ2 in individuals suffering from asthma.
Predict a possible association between the studied genotypes and the development of the disease. |
not specified |
ADRẞ2 |
Arg16Gly
Gln27Glu |
Asthma |
It was found an association between the 27bp repeat polymorphism of the eNOS gene and susceptibility to asthma.
The prevalence of the Arg and Gly alleles of the ADRẞ2 Arg16Gly polymorphism in asthmatics is 68.3% and 31.7%, respectively.
In the ADRẞ2 Gln27Glu polymorphism, the prevalence in mutated allele (Glu) in asthma patients is higher than in the wild allele (Gln).
No association was found between eNOS or ADRβ2 polymorphisms and response to therapeutics. |
[49] |
eNOS |
Master’s Thesis
|
Revision work about the importance of pharmacogenetics in rheumatoid arthritis.
Identified the main polymorphisms that may influence the efficacy, safety and applicability of this knowledge in clinical practice. |
Immunosuppressants |
|
Rheumatoid arthritis |
Clinical pharmacogenetic testing is used only with AZA. The SSZ genotyping has the potential to identify patients with greater susceptibility to toxicity.
More studies are needed for the methotrexate and biological agents in order to clarify the mixed and contradictory results of the current studies. |
[50] |
antirheumatic agents
anti-TNF
azathioprine
methotrexate
sulfasalazine |
300 healthy individuals /Center region
Original article |
To characterize CYP2D6 polymorphisms and predict metabolic profiles in the Portuguese population. |
not specified |
CYP2D6*1
CYP2D6*2
CYP2D6*4
CYP2D6*10 |
Drug metabolism |
Higher frequency of CYP2D6*10, and lower frequency of CYP2D6*6, and duplication of *1 and *2 compared to European population.
Important data in terms of effectiveness and safety in the exposure to xenobiotics, and in personalized pharmacotherapy.
|
[33] |
Master’s Thesis
|
Revision work about the studies that demonstrate the influence of polymorphisms in the treatment of tuberculosis, aimed at the Caucasian / Portuguese population. |
not applied |
CYP2E1
GSTM1
GSTT1 |
Tuberculosis |
The genotyping of certain enzymes may bring benefits not only in reducing complications and side effects, but in reducing appointments and hospitalizations. |
[51] |
101 patients
Madeira region
Doctoral Thesis
|
Analysis of multiple environmental factors assessed by questionnaire and the genotyping of SNPs IL131c.144 G/A, IL41590 C/T, IL41RP2 253183, ADRB21c.16 A/G, ADAM33-V4 C/G, ADAM33-S1 c.710 G/A, GSDML1236 C/T and STAT6121 C/T in a sample of Madeiran asthmatic patients and their families, and their association to asthma susceptibility and severity was assessed. |
not applied |
IL131-c.144 G/A
IL4-590 C/T
IL4RP2 253183
ADRB2-c.16 A/G
ADAM33-V4 C/G
ADAM33-S1 c.710 G/A
GSDML-236 C/T
STAT6-21 C/T |
Asthma |
IL41590*T, IL41RP2*183 as well as the combined genotypes IL41590*CT/IL41590*TT and IL41RP2*253183/IL41RP2*253183 were associated to both asthma susceptibility and severity.
GSDML1236*TT was found associated only to asthma severity.
ADAM331-V4*C was significantly over transmitted to asthmatic offspring being linked with the disease.
The findings suggest that in addition to environmental influences, IL41590 C/T, IL41RP2 253183, ADAM331V4 C/G and GSDML1236 C/T SNPs may constitute important genetic factor contributing to asthma susceptibility and/or severity in Madeira population. |
[52] |
25 patients / not specified
Original article
Only Genotyping |
To study the association of HLA-B*58:01 with allopurinol-induced sCADR in a Portuguese population. |
Antigout preparations |
HLA-B*58:01 |
DRESS
SJS / TEN
|
HLA-B*58:01 was present in 16 patients with sCADR (64%) [12 DRESS (63%), four SJS/TEN (67%)], one allopurinol-tolerant individual (4%) and 63 normal controls.
When compared with the normal population, HLA-B*58:01 was associated with a higher risk of sCADR, both DRESS and SJS/TEN.
There was no statistically different risk between the 2 types of CADR.
Portuguese patients with sCADR from allopurinol, both DRESS and SJS/TEN, have a high frequency of HLA-B*58:01, with an OR similar to European patients with SJS/TEN. |
[34] |
Allopurinol
|
Master’s Thesis |
A bibliographic review focus on pharmacogenetics and HIV therapy, looking closely at several types of antiretroviral drugs: the nucleotide reverse transcriptase inhibitors, the non-nucleotide reverse transcriptase inhibitors and the protease inhibitors and the way that several genes change the therapeutical response. |
Antiretrovirals |
|
HIV therapy |
There is still a large amount of information that needs to be investigated and understood in relation to the possible interactions between genotypes, pharmacokinetics and pharmacodynamics of antiretrovirals.
Genetic variants are responsible for inter-individual variability, regarding the effectiveness of antiretroviral treatment and in the emergence of adverse reactions. |
[62] |
CCR5 antagonists
Fusion inhibitors
Integrase inhibitors
|
116 patients
70 Portuguese non-Gypsy (control group)
/ not specified
Master’s Thesis
Only Genotyping |
To characterise a sample of Portuguese Gypsies for a selected panel of SNPs in genes with pharmacogenetic relevance, and to compare the derived pharmacogenetic profile with that of the Portuguese host population. |
not specified |
CYP2C9 |
rs1799853
rs1057910 |
Drug metabolism |
For the screened variations no departures from Hardy-Weinberg equilibrium were detected in the Portuguese Gypsy and Portuguese non-Gyspy populations.
No major differences were detected in the results of the 2 populations. |
[55] |
CYP2C19 |
rs4244285 |
NAT2 |
rs1041983
rs1801280 |
TPMT |
rs1800462
rs1800460
rs1142345
rs56161402 |
VKORC1 |
rs9923231 |
51 patients / Centre
Master’s Thesis
Only Genotyping |
To characterize a sample of Portuguese diabetic individuals, through survey of a single nucleotide polymorphisms set identified in the literature and databases (related to pharmacogenetics of DM2 in coding region and for the European population (EUR)), followed by a correlation of the results with the drugs administered to individuals in the sample.
To propose a set of SNPs candidates for pharmacogenetics of DM2.
|
Sulphonylureas Glibenclamida
Gliclazida
Glimepirida
Sulphonylureas
Tolbutamida
Tolbutamida |
ABCC8 |
rs1799859
rs1801261 |
Diabetes Mellitus type 2 (DM2) |
There were identified SNPs associated with pharmacogenetics of DM2 in scientific articles and databases, where a total of 98 SNPs were identified.
The SNPs were filtered for those in the coding region and associated with the EUR population.
Sixteen SNPs were observed in 10 genes in the 51 patients.
Correlation of drugs administered in the sample in study with the results from the survey of these SNPs, indicated that individuals carrying the SNPs rs12208357, rs34130495 and rs3405950 (SLC22A1) needed a higher dose of metformin, the carriers of SNP rs1801282 (PPAR) needed tighter control treatment metformin (given the increased risk of failure for this treatment) and carriers of SNP rs5219 (KCNJ11) needed a higher dose of gliclazide.
It was proposed a set of potential SNPs candidates for future studies concerning the pharmacogenetics of DM2 in the Portuguese population 32 SNPs located in the coding region and not yet referenced in the EUR population were selected from the set of 98 SNPs.
Additional 15 SNPs not yet related to the DM2 were also identified in the 51 patients. |
[53] |
CYP2C9
|
rs1799853
rs1057910 |
IRS1 |
rs1801278 |
KCNJ11 |
rs5219 |
Meglitinides |
|
Repaglinida
Nateglinida
|
CYP2C8 |
rs10509681
rs11572080 |
CYP2C9 |
rs1057910 |
SLCO1B1 |
rs4149056
rs2306283 |
Thiazolidinediones |
|
Rosiglitazona
Pioglitazona |
CYP2C8 |
rs10509681
rs11572080 |
Biguanides |
|
Metformina |
SLC22A1 |
rs72552763
rs35167514
rs12208357
rs34130495
rs34059508
rs1867351 |
PPARγ |
rs1801282 |
Inibitors of α glicosidase |
|
Acarbose |
PGC-1α (PPARGC1A) |
rs8192678
|
GLP-1 and analogues |
|
GLP-1 |
THADA |
rs7578597 |
Master’s Thesis
|
A review work that aimed at present an overview on the state of the art of pharmacogenomics, with the introduction of its basic concepts, how genetic polymorphisms may modulate individual’s susceptibility to certain diseases or influences the therapeutic efficacy and safety of drugs. |
not applied |
|
|
It was concluded that Pharmacogenomics has reached a state in which it makes possible, if not an individual tuning of the pharmaceutical regímen, at leats the definition of groupings of individuals with similar genetic profiles and a corresponding more homogeneous response to drugs. |
[54] |
242 patients
/Center
Original article
Only Genotyping |
To identify clinical and/or genetic predictors of response to several therapies in Crohn’s disease (CD) patients. |
Immunosuppressants |
ABCB1 C3435T, G2677T/A IL23R G1142A
C2370A
G9T
CASP9 C93T
Fas G670A
LgC844T
ATG16L1 A898G |
Crohn’s disease |
Older patients responded better to 5-aminosalicylic acid (5-ASA) and to azathioprine while younger ones responded better to biologicals.
Previous surgery negatively influenced response to 5-ASA compounds but favoured response to azathioprine.
Heterozygotes for ATGL16L1 SNP had a significantly higher chance of responding to corticosteroids, while homozygotes for Casp9 C93T SNP had a lower chance of responding both to corticosteroids and to azathioprine.
TT carriers of ABCB1 C3435T SNP had a higher chance of responding to azathioprine, while carriers of ABCB1 G2677T/A SNP, as well as responding better to azathioprine, had a lower chance of responding to biologicals, which became significant after adjusting for gender. |
[35]
|
Azathioprine |
Biologicals
Corticosteroids
|
Cohort
Original article |
To elucidate the role of methylenetetrahydrofolate reductase (MTHFR) C677T and aminoimidazole carboxamide adenosine ribonucleotide transformylase (ATIC) T675C polymorphisms and clinicopathological variables in clinical response to MTX in Portuguese rheumatoid arthritis (RA) patients. |
Methotrexate |
MTHFR C677T
ATIC T675C |
Rheumatoid Arthritis |
MTHFR 677TT and ATIC 675T carriers were associated with over 4-fold increased risk for nonresponse.
For clinicopathological variables, noncurrent smokers, patients positive to anti-cyclic citrullinated peptide and antinuclear antibodies, with higher health assessment questionnaire score, and nonsteroidal anti-inflammatory drug users were also associated with nonresponse.
Subcutaneous administration route was associated with response.
MTHFR C677T and ATIC T675C genotyping combined with clinicopathological data may help to identify patients who will not benefit from MTX treatment and, therefore, assist clinicians in personalizing RA treatment. |
[36] |
233 Caucasian /
North region
Original article |
To elucidate the influence of TYMS polymorphisms in MTX therapeutic outcome (regarding clinical response and toxicity) in Portuguese RA patients. |
Methotrexate |
TYMS |
rs34743033
rs2853542
rs34489327 |
Rheumatoid Arthritis |
TYMS polymorphisms could be important to help predicting clinical response to MTX in RA patients.
Translation into clinical practice needs larger studies to confirm the evidences. |
[37] |
233 patients
North region
Original article
|
To evaluate the influence of single nucleotide polymorphisms (SNPs) in genes encoding for MTX transporters with the occurrence of MTX-related toxicity (overall and gastrointestinal). |
Methotrexate |
SLC16A7 |
rs3763980
rs10877333 |
Rheumatoid Arthritis |
SLC19A1, SLC46A1 and SLCO1B1 genotypes may help to identify patients with increased risk of MTX-related overall toxicity and that SLC19A1 and SLCO1B1 genotypes, and SLC19A1 haplotypes may help to identify patients with increased risk of MTX-related gastrointestinal toxicity. |
[38] |
SLC19A1 |
rs7499
rs1051266
rs2838956
rs3788200 |
SLC22A6 |
rs11568626 |
SLC22A11 |
rs11231809 |
SLC46A1 |
rs2239907 |
SLCO1B1 |
rs4149056 |
ABCB1 |
rs1045642
rs1128503
rs2032582 |
ABCC1 |
rs35592
rs246240
rs2074087
rs2230671
rs3784864 |
ABCC2 |
rs717620
rs4148396 |
ABCG2 |
rs2231142
rs13120400
rs17731538 |
Master’s Thesis |
A review work about Pharmacogenomics of addiction |
not applied |
SNP
VNTR |
Drug addiction |
Drug addiction remains an unsolved health issue and has limited treatment options currently available.
The existing medications were not developed having a thorough knowledge of genetic and neurobiological causes of the disease.
More replication data is needed concerning some genetic variants to allow the identification of functional variants, but also the need for larger population samples has become clear for detecting small effect variants from the many genes accountable for addiction. |
[56] |
Master’s Thesis |
A bibliographic review on pharmacogenetics in the treatment of breast cancer.
To study of the influence that genetic polymorphisms of metabolic enzymes, efflux transporters and estrogen receptors, have on response to tamoxifen therapy for breast cancer |
not applied |
CYP2C19*2
CYP2C19*17
CYP3A4
CYP3A4*22
CYP3A4*1B
CYP3A5
SULT1A1
SULT1A1*2 |
Breast cancer |
Studies that analysed the role of CYP2D6 genotype in response to tamoxifen are controversial, most of these argue that poor metabolizers and intermediate have worse results than extensive metabolizers, although in only one of the studies with higher impact the same association was observed.
In the CYP3A4, the T allele for the CYP3A4*22 polymorphism was associated with higher concentration of tamoxifen and its metabolites and CYP3A4*1B polymorphism was associated with increased risk of developing endometrial cancer.
The polymorphisms at the estrogen receptors have demonstrated an important role in modulating the response to tamoxifen treatment on regards secondary and adverse effects. Larger population and greater control over variables are needed to reach a personalized medicine. |
[57] |
Lisbon
Porto
Coimbra
Master’s Thesis |
Evaluation of pharmacogenomics in Portuguese clinical practice, identification of the skills and techniques for the application of pharmacogenomics and the potential areas of pharmacogenomics in clinical practice. |
Azathioprine |
not specified |
Oncology and
infectious diseases
|
Pharmacogenomics/genetics in Portugal has some degree of weakness; is not a routine in clinical practice, not well known among professionals, genetics is not mainly use for therapeutic purposes.
The service of IPO Lisbon uses de detection of Human Epidermal growth factor Receptor-type 1 (HER1) for specific therapeutics of breast cancer. |
[58] |
Original article
|
To revise the major definitions in the pharmacogenetics as well as some classic examples of its application (related to cytochrome P450 genes, NAT2 gene and the Cholinesterase gene; the multitude of existing drug targets, like in case of G6PD gene, and the VKORC1 gene). |
not applied |
P450 genes
NAT2
G6PD VKORC1 |
not applied |
Pharmacogenetics contribute to the development of new drugs, since it gives an important data, namely the knowledge of the potential variability associated with metabolization and/or action of the drug.
In addition, pharmacogenetics also plays an important role in reducing the number of patients who must participate in clinical trials, and potentially reduce the risk of failure in the lead-up stages in the market. |
[39] |
52 individuals with a suggestive phenotype of
trimethylaminuria and 100 healthy individuals/ not specified
Original article
Only Genotyping |
Portuguese patients with phenotype suggestive of TMAu were evaluated for molecular screening of the FMO3 gene. |
not specified
|
FMO3 |
TMAu |
Identification of 32 variants in the FMO3 coding region.
P.Glu158Lys and p.Glu308Gly polymorphisms, in combination with other variants, originate different phenotypic patterns, which may lead to an abnormal drug metabolism in the liver and other organs and tissues. |
[40] |
208 patients / South region
Original article
Genotyping and drug testing
|
To assess the pharmacogenetic profile of a South Portuguese population according
to established dosing guidelines for commonly prescribed drugs and to compare it with that of previously genotyped populations. |
Thiopurines
Clopidogrel
Warfarin
Fluoropyrimidines
Irinotecan
Codeine
Tricyclics |
ABCB1 |
rs1045642
rs1128503
rs2032582 |
Drug metabolism
|
It was found a significant small differentiation between the Portuguese regional populations regarding CYP2C9 rs1057910, CYP2D6 rs3892097, MTHFR rs1801133 and F5 rs6025.
When considering 4 HapMap populations, ADH1B rs2066702, ADH1B rs1229984, NAT2 rs1799931 and VKORC1 rs9923231 displayed a significant population differentiation.
18.9% of the participants are intermediate or poor metabolizers for at least 3 drugs simultaneously and that 84.6% of the participants have at least one therapeutic failure or ADR risk allele for the considered drugs.
There is a high prevalence of risk alleles associated with an altered drug metabolism regarding drugs largely used by the South Portuguese population. |
[41]
|
ADH1B |
rs1229984 |
ADH1C |
rs698 |
ADRB2 |
rs1042714 |
COMT |
rs4680 |
CYP2C19 |
rs4244285
rs4986893 |
CYP2C8 |
rs11572080 |
CYP3A5 |
rs776746 |
CYP2D6 |
rs3892097 |
DPYD |
rs67376798
rs1801265
rs55886062 |
F5 |
rs6025 |
GSTP1 |
rs1695 |
KCNJ11 |
rs5219 |
TPMT |
rs1800462
rs1800460
rs1800584
rs1142345 |
233 patients /North
Original article
Genotyping and drug testing
|
Clinicopathological data from rheumatoid arthritis patients treated with methotrexate were collected, clinical response defined, and patients genotyped for 23 single nucleotide polymorphisms.
Genotype and haplotype analyses were performed using multivariate methods and a genetic risk index for non-response was created |
Immunosuppressants
Antimetabolites |
SLC16A7 |
rs3763980
rs10877333 |
Rheumatoid Arthritis |
Genetic polymorphisms in SLC22A11 and ABCC1 could be predictors of clinical response to methotrexate in Portuguese rheumatoid arthritis patients.
Genotyping patients according to these genetic markers may be helpful to identify which patients will not benefit from methotrexate treatment, highlighting the relevance of developing the field of personalized medicine. |
[42] |
Methotrexate; Methotrexate + drug panel |
SLC19A1
|
rs7499
rs1051266
rs2838956
rs3788200 |
SLC22A11 |
rs11231809 |
SLC46A1 |
rs2239907 |
SLCO1B1 |
rs4149056 |
167 patients
Original article
Genotyping and drug testing
|
To evaluate the repercussion of personalization of INH dosing by NAT2 genotyping in the management of tuberculosis patients.
To assess the role of other candidate genes like CYP2E1, GSTM1 and GSTT1 encoding detoxifying enzymes, and ABCB11, encoding a protein involved in bile salt transport. |
Antimycobacterials |
NAT2
CYP2E1
GSTM1
GSTT1
ABCB11 |
|
Tuberculosis |
Clinical variables such as gender and age were not associated with the occurrence of INH-induced hepatitis.
Slow acetylators (52.3%), identified by NAT2 genotyping, were significantly more prone to develop, as well as homozygous for variant Ala of ABCB11 polymorphism (rs2287622).
The presence of both risk genotypes was also significantly associated with increased susceptibility to hepatotoxicity.
Risk genotypes were frequent among patients: 52% of SA (NAT2), 32% of Ala/Ala (ABCB11) and 21% with both risk genotypes. |
[43]
|
Isoniazid
|
Master’s Thesis |
To develop a Sanger sequencing methodology for CYP2D6 gene to identify genetic variants that cause absence of enzyme activity and its application to post-mortem cases with tramadol |
Tramadol |
CYP2D6 |
|
|
The methods were successfully applied to post mortem blood samples.
Alleles and genotype frequencies were in accordance with the expected for European population.
Tramadol metabolism, expressed as its metabolites concentration ratio (N-desmethyltramadol/O-desmethyltramadol), has been shown to be correlated with the predicted phenotypes based on genetic characterization.
This is presumably the first time that a CYP2D6 sequencing methodology is validated and applied to post-mortem samples, in Portugal. |
[59] |
56 Portuguese gypsies / not specified
Master’s Thesis
Only Genotyping |
To characterize the Portuguese Roma for Single Nucleotide Polymorphisms (SNPs), relevant from the Pharmacogenetics point of view.
To evaluate if the Roma show any peculiarity regarding drug response, in comparison with the host population. |
not specified |
CYP2D6 |
rs1065852
rs28371706
rs61736512
rs3892097
s35742686
rs5030656
rs16947
rs28371725
rs59421388
rs1135840 |
Drug metabolism
|
For the variations studied, only one SNP revealed significant deviation from the Hardy – Weinberg expectation, even after the Bonferroni correction, which was the 4180 G>C.
Comparatively to the Portuguese host population, the Roma showed some differences, especially an increased frequency of the CYP2D6*4, an allele implying null enzymatic activity.
Regarding the theoretical metabolic profiles, differences were found, especially the IM and PM profiles. |
[60] |
1688 patients / North, Centre, South regions
Original article
Genotyping and drug testing
|
To determine the prevalence of genotypes associated with a lower efficacy or a higher risk of adverse side effects in the treatment with statins in the Portuguese population.
Several SNPs involved in the metabolism, absorption, transport and/or excretion of the various types of statins were genotyped. |
Statins
|
SLCO1B1 |
rs4149056 |
Dyslipidaemia |
The SLCO1B1*5 variant, associated with an increased risk of developing myopathy on simvastatin treatment, has a frequency 2 times higher in the sample than described in the population databases. This fact, coupled with the large increase in national consumption of statins, mainly simvastatin, is an important factor that should be considered in the decision-making of the prescription of antidislipidemics. |
[44] |
APOE |
rs7412 |
ABCB1 |
rs2032582 |
KIF6 |
rs20455 |
HMGCR |
rs17238540 |
POR |
rs1057868 |
ABCB1 |
rs1045642 |
CYP3A5 |
rs776746 |
CYP2C9 |
rs1057910 |
Master’s Thesis |
To relate the knowledge underlying the field of Pharmacogenetics with pharmaceutical activity in the hospital context, reviewing the most important topics in this area for hospital pharmaceutical practice. |
not specified |
|
Oncology |
The pharmacist assumes a central role in the implementation of Pharmacogenetics in clinical practice, since is a health professional with basic knowledge important for understanding this area, having the duty to specialize and help to instruct the remaining members of the research team health about the correct interpretation of the results of pharmacogenetic tests and the best way to apply them. |
[61] |
Original article |
To investigate the impact of CYP2D6 genotyping of the tamoxifen metabolizing enzymes in the clinical management of breast cancer patients. |
Tamoxifen |
CYP2D6 |
Breast cancer |
Portugal presents an interesting case for comparison in international pharmacogenomics context. This is especially the case of CYP2D6 testing prior to tamoxifen therapeutics. This is because there are no implemented measures based on pharmacogenomics analysis prior to therapy. Changing clinical paradigms involves assessment of several factors and a country with a clinical context as that of Portugal might function as a sample control in such analysis. |
[46] |
Original article
Genotyping and drug testing
|
To report on the real-life experience of 2 Portuguese dermatology departments with ustekinumab in patients with moderate to severe psoriasis.
To identify the clinical characteristics associated with a weaker clinical response. |
Immunosuppressants |
HLACw*0602 |
Psoriasis |
A PASI75 therapeutic response was observed in 67.2%, 85.3%, 89.6% and 88.7% of patients at weeks 4, 12, 24 and 52, respectively.
Neither cardiovascular events nor cases of reactivation of previous infections (tuberculosis, hepatitis B) were observed during follow-up.
The therapeutic response was higher in patients naïve to biologic therapies as compared to non-naïve patients.
A trend towards lower clinical response was observed in patients weighing between 90-100 kg, and dosage optimization in these patients may be of value prior to considering biologic switch. |
[45] |
Ustekinumab
|