Dual approaches in pharmacogenetics: Developing PCR-SSP and RT-PCR methods for HLA-B*13:01 screening to prevent dapsone and Co-trimoxazole SCARs.

Dapsone and co-trimoxazole are potent antibiotics for treating various infections and inflammations. However, several studies reported the strongly association between severe cutaneous adverse drug reactions (SCARs) to both drugs and the HLA-B*13:01 allele. Rapid and reliable screening for the HLA-B*13:01 allele can mitigate the risk of dapsone-induced SCARs.

Complete mitochondrial genomes of patients from Thailand with cardiovascular diseases.

Several previous studies have reported that both variation and haplogroups of mitochondrial (mt) DNA were associated with various kinds of diseases, including cardiovascular diseases, in different populations, but such studies have not been carried out in Thailand. Here, we sequenced complete mtDNA genomes from 82 patients diagnosed with three types of cardiovascular disease, i.e.

Association between alleles and beta-lactam antibiotics-related severe cutaneous adverse reactions.

Beta-lactam antibiotics are one of the most common causes of antibiotics-related severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reactions with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Recent evidence demonstrated that the human leukocyte antigen () polymorphisms play important roles in the development of drug-related SCARs. This study aimed to extensively characterize the associations between genetic polymorphisms and several phenotypes of SCARs related to beta-lactam antibiotics.

Associations of HLA and drug-metabolizing enzyme genes in co-trimoxazole-induced severe cutaneous adverse reactions.

Co-trimoxazole is mainly used as a first-line drug for treatment and prophylaxis against Pneumocystis jiroveci pneumonia. This drug, however, has been reported as the most common causative drug for severe cutaneous adverse reactions (SCARs). This study aimed to extensively elucidate the associations between genetic polymorphisms of HLA class I and genes involved in bioactivation and detoxification of co-trimoxazole on co-trimoxazole-induced SCARS in a large sample size and well-defined Thai SCARs patients.

Development of label-free electrochemical impedance spectroscopy for the detection of HLA-B*15:02 and HLA-B*15:21 for the prevention of carbamazepine-induced Stevens-Johnson syndrome.

Background: Carbamazepine (CBZ) is an FDA-approved anticonvulsant that is widely used to treat epilepsy, bipolar disorder, trigeminal neuralgia and chronic pain. Several studies have reported a strong association between HLA-B*15:02 and carbamazepine-induced Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). However, the HLA-B75 serotype (HLA-B*15:02, HLA-B*15:08, HLA-B*15:11 and HLA-B*15:21) has been found in patients with carbamazepine-induced SJS/TEN.

NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine.

6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP.

Meta-Analysis of Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations.

The high incidence of thiopurine-induced myelosuppression in Asians is known to be attributable to genetic variation in thiopurine metabolism. A quantitative synthesis to summarize the genetic association with thiopurine-induced myelosuppression in Asians was therefore conducted. A Literature search was performed from January 2016 to May 2021 in the following databases: PubMed, Web of Science, and Embase and addition search included the studies from Zhang et al.

The Thai reference exome (T-REx) variant database.

To maximize the potential of genomics in medicine, it is essential to establish databases of genomic variants for ethno-geographic groups that can be used for filtering and prioritizing candidate pathogenic variants. Populations with non-European ancestry are poorly represented among current genomic variant databases. Here, we report the first high-density survey of genomic variants for the Thai population, the Thai Reference Exome (T-REx) variant database.

Is a Predictive Marker of Dapsone-Induced Severe Cutaneous Adverse Reactions in Thai Patients.

allele has been identified as the genetic determinant of dapsone hypersensitivity syndrome (DHS) among leprosy and non-leprosy patients in several studies. Dapsone hydroxylamine (DDS-NHOH), an active metabolite of dapsone, has been believed to be responsible for DHS. However, studies have not highlighted the importance of other genetic polymorphisms in dapsone-induced severe cutaneous adverse reactions (SCAR).

Characterization of T-Cell Responses to SMX and SMX-NO in Co-Trimoxazole Hypersensitivity Patients Expressing .

-positive patients in Thailand can develop frequent co-trimoxazole hypersensitivity reactions. This study aimed to characterize drug-specific T cells from three co-trimoxazole hypersensitive patients presenting with either Stevens-Johnson syndrome or drug reaction with eosinophilia and systemic symptoms. Two of the patients carried the HLA allele of interest, namely .

Genetic Polymorphisms of Drug-Metabolizing Enzymes Involved in 6-Mercaptopurine-Induced Myelosuppression in Thai Pediatric Acute Lymphoblastic Leukemia Patients.

Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 ( ) genes have been proposed as key determinants of 6-mercaptopurine (6-MP)-induced myelosuppression in pediatric acute lymphoblastic leukemia (ALL). In the present study, genotypes of and were investigated in 178 Thai pediatric patients with ALL by the TaqMan SNP genotyping assay and DNA sequencing. The frequency of was 0.

Identification of drug-specific public TCR driving severe cutaneous adverse reactions.

Drug hypersensitivity such as severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), could be life-threatening. Here, we enroll SCAR patients to investigate the T cell receptor (TCR) repertoire by next-generation sequencing. A public αβTCR is identified from the cytotoxic T lymphocytes of patients with carbamazepine-SJS/TEN, with its expression showing drug/phenotype-specificity and an bias for HLA-B*15:02.

Roles of pharmacogenomics in non-anthracycline antineoplastic-induced cardiovascular toxicities: A systematic review and meta-analysis of genotypes effect.

Background: Exploration on genetic roles in antineoplastic-related cardiovascular toxicity has increased with the advancement of genotyping technology. However, knowledge on the extent of genetic determinants in affecting the susceptibility to the cardiovascular toxicities of antineoplastic is limited. This study aims to identify potential single nucleotide polymorphism (SNP) in predicting non-anthracycline antineoplastic-related cardiovascular toxicity.

HLA Alleles and CYP2C9*3 as Predictors of Phenytoin Hypersensitivity in East Asians.

To develop a pre-emptive genetic test that comprises multiple predisposing alleles for the prevention of phenytoin-related severe cutaneous adverse reactions (SCARs), three sets of patients with phenytoin-SCAR and drug-tolerant controls from Taiwan, Thailand, and Japan, were enrolled for this study. In addition to cytochrome P450 (CYP)2C9*3, we found that HLA-B*13:01, HLA-B*15:02, and HLA-B*51:01 were significantly associated with phenytoin hypersensitivity with distinct phenotypic specificities. Strikingly, we showed an increase in predictive sensitivity of concurrently testing CYP2C9*3/HLA-B*13:01/HLA-B*15:02/HLA-B*51:01 from 30.

Pharmacogenetic Markers of Drug Hypersensitivity in a Thai Population.

Severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS) are potentially life-threatening cutaneous reactions caused by several drugs. Recently, a number of genes encoding for human antigen presenting proteins, alleles, have been discovered as valid pharmacogenetic markers for prediction of these life-threatening reactions. This study was aimed to determine the distribution of alleles including the class I and class II genes in 183 unrelated individuals of a Thai population using high resolution genotyping in order to obtain 2-field data (4-digit resolution) and compare the frequencies of the alleles that have been proposed as markers of SCARs with other ethnics.

The Medication Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Asians: The Major Drug Causality and Comparison With the US FDA Label.

Specific ethnic genetic backgrounds are associated with the risk of Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017.

Effect of coenzyme Q10 on mitochondrial respiratory proteins in trigeminal neuralgia.

Trigeminal neuralgia (TN) is the neuropathic pain. Mitochondrial dysfunction, increased oxidative stress, and inflammation demonstrated in chronic pain. Carbamazepine (CBZ) is the first-line drug for TN, however, it is still insufficient.

Comparison between the Allele and Single-Nucleotide Polymorphisms in Chromosome 6 for Prediction of Allopurinol-Induced Severe Cutaneous Adverse Reactions.

Severe cutaneous adverse drug reactions (SCARs) are life-threatening reactions. The strong association between the allele and allopurinol-induced SCARs is well recognized. Screening for allele before prescribing allopurinol in some populations has been recommended.

Association of and Alleles with Lamotrigine-Induced Cutaneous Adverse Drug Reactions in the Thai Population.

Lamotrigine (LTG) is commonly used for treatment of epilepsy and bipolar disorder. It is one of the common cause of cutaneous adverse drug reactions (CADR). Clinical symptoms of LTG-induced CADR range from maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCAR).

Cost-effectiveness analysis of HLA-B*58: 01 genetic testing before initiation of allopurinol therapy to prevent allopurinol-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in a Malaysian population.

Objective: Studies found a strong association between allopurinol-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and the HLA-B*58:01 allele. HLA-B*58:01 screening-guided therapy may mitigate the risk of allopurinol-induced SJS/TEN. This study aimed to evaluate the cost-effectiveness of HLA-B*58:01 screening before allopurinol therapy initiation compared with the current practice of no screening for Malaysian patients with chronic gout in whom a hypouricemic agent is indicated.