Association between Genetic Polymorphism of SCN1A, GABRA1 and ABCB1 and Drug Responsiveness in Vietnamese Epileptic Children.

Background and Objectives: Drug resistant epilepsy (DRE) is a major hurdle in epilepsy, which hinders clinical care, patients' management and treatment outcomes. DRE may partially result from genetic variants that alter proteins responsible for drug targets and drug transporters in the brain. We aimed to examine the relationship between SCN1A, GABRA1 and ABCB1 polymorphism and drug response in epilepsy children in Vietnam. Materials and Methods: In total, 213 children diagnosed with epilepsy were recruited in this study (101 were drug responsive and 112 were drug resistant). Sanger sequencing had been performed in order to detect six single nucleotide polymorphisms (SNPs) belonging to SCN1A (rs2298771, rs3812718, rs10188577), GABRA1 (rs2279020) and ABCB1 (rs1128503, rs1045642) in study group. The link between SNPs and drug response status was examined by the Chi-squared test or the Fisher's exact test. Results: Among six investigated SNPs, two SNPs showed significant difference between the responsive and the resistant group. Among those, heterozygous genotype of SCN1A rs2298771 (AG) were at higher frequency in the resistant patients compared with responsive patients, playing as risk factor of refractory epilepsy. Conversely, the heterozygous genotype of SCN1A rs3812718 (CT) was significantly lower in the resistant compared with the responsive group. No significant association was found between the remaining four SNPs and drug response. Conclusions: Our study demonstrated a significant association between the SCN1A genetic polymorphism which increased risk of drug-resistant epilepsy in Vietnamese epileptic children. This important finding further supports the underlying molecular mechanisms of SCN1A genetic variants in the pathogenesis of drug-resistant epilepsy in children.

Application of the sustainable system-of-systems approach and econometric analysis to address China's decarbonisation problem.

The Sustainable system-of-systems (SSoS) approach, complemented with econometric analysis was used to address China's decarbonisation problem, i.e. selecting fossil fuel consumption sources to be reduced in various regions to meet CO2 reduction targets with minimal effect on population and economic growth. In the SSoS, the micro-level system is represented by residents' health expenditure, the meso-level system by industry's CO2 emissions intensity, and the macro-level system by the government's achievement of economic growth. Regional panel data from 2009 to 2019 were used in an econometric analysis conducted using structural equation modelling. The results show that health expenditure was affected by CO2 emissions from the consumption of raw coal and natural gas. To support economic growth, the government should reduce raw coal consumption. For CO2 emissions reduction, industry in the eastern region should reduce raw coal consumption. The key advantage is SSoS with econometrics offers a way to reach a common goal among stakeholders.Practitioner summary: This research shows that the use of the SSoS approach, complemented with an econometric analysis of key social, economic, and natural capital data, can address a complex decarbonisation problem facing a nation (China, in the present case) while considering the goals of all stakeholders (the government, industrial communities, and residential communities).Abbreviations: CEADs: Carbon Emissions Accounts and Datasets for Emerging Countries; CEIC: CEIC Global Database; GRPS: World Economic Forum's Global Risks Perception Survey; HFE: human factors/ergonomics; ML-SEM: maximum likelihood estimation method; NDRC: National Development and Reform Commission of China; SEM: structural equation modelling; SSoS: Sustainable system-of-systems; TBL: triple bottom line.

A case report of Cronkhite-Canada syndrome first encounterd at a hospital in northern Vietnam.

Introduction and importance: Cronkhite-Canada syndrome (CCS) is an extremely rare non-inherited syndrome first described in 1955 with only about 500 more cases reported so far. Since the aetiology of the disease remains unknown, there were no specific treatments in consensus. In many countries, CCS is a completely new condition that may confuse physicians at first encounter. Lessons should be learned from these cases by gastrointestinal specialists to be aware of this condition in any circumstances. Case presentation: The authors reported a case study of a 45-year-old Vietnamese male with CCS diagnosis, which encountered at our centre for the first time. Clinical discussion: The definitive diagnosis was provided by combining clinical characteristics, and endoscopic and histopathologic features, after excluding other causes of gastrointestinal polyposis. The patient responds to corticosteroids, proton pump inhibitors, and nutritional support right after treatment. After 1 year of treatment, his symptoms ameliorated completely although colon polyps insignificantly reduced. Conclusion: Gastroenterologists should always be aware of patients with CCS with the following symptoms: gastrointestinal hamartomatous polyps, diarrhoea, and the dermatologic triad of alopecia, hyperpigmentation, and onychodystrophy.

Copy number variations of cytochrome P450 genes in Kinh Vietnamese.

Background: The cytochrome P450 (CYP450) family is well known as a major group of drug metabolizing enzymes. The polymorphism of CYP450 genes is the main factor having an impact on the interindividual difference in drug response, including drug efficacy and drug safety. The single nucleotide polymorphism (SNPs) of Vietnamese Kinh has been widely studied, but information about the copy number variations (CNVs) of other CYP450 genes is still unknown. Objective: To identify the CNV variability of CYP450 in 154 healthy unrelated Kinh Vietnamese, except eCYP2D6, which was previously reported. Methods: Multiplex Ligation-Dependent Probe Amplification (MLPA) was applied for determination of copy number of 10 CYP450 genes. Later, PCR or quantitative PCR (qPCR) was used to confirm the detected CNVs in randomly chosen subjects. Results: Of the 154 subjects, along with CYP2D6, 4 other CYP450 genes showed CNVs including duplications (CYP1B1), deletions (CYP2A6 and CYP2C9), and both duplications and deletions (CYP2E1). Among these, CYP2A6 exhibited the greatest frequency of CNVs compared with other CYP450, in which CYP2A6Del accounted for 11%. Meanwhile, allele CYP2E1Del showed the lowest frequency with only 0.3%. Conclusions: The present study provides new insight into CYP450 CNVs in the Kinh Vietnamese cohort. Our data have contributed to genetic profiling of CYP450 CNVs in Vietnam, which would be helpful for facilitating implementation of pharmacogenetics in drug dosing adjustment in Vietnam.

Common mental health disorders in adults with inflammatory skin conditions: nationwide population-based matched cohort studies in the UK.

BACKGROUND: Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk. METHODS: We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997-2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids). RESULTS: We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13-1.16], psoriasis 1.17 [1.15-1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1-1.12], psoriasis 1.21 [1.19-1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry. CONCLUSIONS: Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management.

Association of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with Alcohol abuse and Alcoholic Cirrhosis in People Living in Northeast Vietnam.

OBJECTIVE: Alcohol abuse can cause developing cirrhosis, even liver cancer. Several single nucleotide polymorphisms (SNPs) of ADH1B, ADH1C, and ALDH2 genes have been reported to be associated with alcohol abuse and alcoholic cirrhosis (ALC). This study investigated the association between three SNPs of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with alcohol abuse and ALC in people living in the Northeast region of Vietnam. METHODS: 306 male participants were recruited including 206 alcoholics (106 ALC, 100 without ALC) and 100 healthy non-alcoholics. Clinical characteristics were collected by clinicians. Genotypes were identified by Sanger sequencing. Chi-Square (χ2) and Fisher-exact tests were used to assess the differences in age and clinical characteristics, Child-Pugh score, frequencies of alleles and genotypes. RESULT: Our data showed that the frequency of ALDH2*1 was significantly higher in alcoholics (88.59%) and ALC groups (93.40%) than that of healthy non-alcoholics (78.50%) with p=0.0009 and non-ALC group (83.50%) with p=0.002, respectively. We detected opposite results when examined ALDH2*2. Frequency of combined genotypes with high acetaldehyde accumulation were significantly lower in alcoholics and ALC group than those of control groups with p=0.005 and p=0.008, respectively. Meanwhile, the proportion of combined genotypes with non-acetaldehyde accumulation were significantly two times higher in the ALC group (19.98%) than those of the non-ALC group (8%) with p=0.035. These combined genotypes showed a decreasing trend in the Child-Pugh score from likely phenotype causing risk for non-acetaldehyde accumulation to high acetaldehyde accumulation. CONCLUSION: The ALDH2*1 allele was found as a risk factor for alcohol abuse and ALC, and combined genotypes of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with non-acetaldehyde accumulation increase ALC risk. In contrast, ALDH2*2 and the genotype combinations related to high acetaldehyde accumulation were protective factors against alcohol abuse and ALC.

A qualitative study on stress, coping strategies and feasibility of music intervention among women with cancer receiving chemotherapy during COVID-19 pandemic in Vietnam.

Breast and gynaecological cancer (BGC) patients receiving chemotherapy may experience high levels of stress during the COVID-19 pandemic. Music interventions may be effective in lowering their stress levels. This study explored stressors, coping strategies, and the feasibility of music interventions among BGC patients in Vietnam. An exploratory qualitative study with individual face-to-face semi-structured interviews was conducted. A convenience sample of BGC patients receiving chemotherapy was recruited from the oncology centre of a public hospital in Vietnam. Twenty patients were interviewed with open-ended questions developed based on the transactional model of stress and coping to explore stress-causing factors and coping strategies and based on guidelines for music therapy practice to explore their music preferences and perceptions. Field notes and interview transcripts were analysed following the qualitative content analysis approach. Two stressor themes were identified: undesirable experiences during treatment and patients' inability to fulfil their own roles and responsibilities. Our findings revealed a new coping strategy-self-realisation of responsibilities towards the family-that is not listed in the transactional model of stress and coping. Future psychological interventions for stress management among BGC patients should focus on raising the patients' awareness of their values and responsibilities towards their families. Three categories of preferred music genres for stress reduction were identified: religious, softly melodic, and revolutionary music. The patients were aware of the positive effects of music and had different musical preferences. This study also explored the acceptance of music interventions and facilitators and barriers to implementing them among BGC patients in Vietnam. The findings suggest that before implementing music interventions, the musical preferences, religions, and beliefs of each individual should be considered to achieve desirable results. Music interventions for BGC patients receiving chemotherapy in Vietnam are feasible. Further intervention studies are needed to evaluate their effectiveness.

LMP1-EBV Gene Deletion Mutations and HLA Genotypes of Nasopharyngeal Cancer Patients in Vietnam.

Nasopharyngeal carcinoma (NPC) is the most common cancer among head and neck cancers in Vietnam. We aimed to identify the rate of a 30 bp deletion mutation of the LMP1-EBV gene in nasopharyngeal biopsy tissue samples, the HLA genotypes of NPC patients, and the relationship between these two targets. Patients with NPC at Can Tho Oncology Hospital from September 2014 to December 2018 were selected. A length of 30 bp of the del-LMP1-EBV gene was analyzed using a PCR technique, and the HLA genotypes in patients' blood samples were analyzed with PCR-SSO technology. HLA-B*15 gene carriers had the highest risk of 30 bp LMP1-EBV gene deletion mutation, which was found in 51 out of 70 patients (72.9%). Carriers of the HLA-B*15 allele had a 4.6-fold increased risk of a 30 bp del-LMP1-EBV gene compared with non-carriers of this allele. The initial identification of NPC was related to the 30 bp del-LMP1-EBV gene and high frequencies of the -A*02, -B*15, -DRB1*12, -DQB1*03, and -DQA1*01 HLA alleles. Our study results suggest an association of the 30 bp del-LMP1-EBV gene and the HLA-B*15 allele with NPC susceptibility.

Single Nucleotide Polymorphisms of ADH1B, ADH1C and ALDH2 Genes in 235 People Living in Thai Nguyen Province of Vietnam.

OBJECTIVE: ADH1B, ADH1C and ALDH2 genes are mainly responsible for alcohol metabolism in the body. Several single nucleotide polymorphisms (SNPs) of these genes have been reported to be associated with alcohol dependence and are considered risk factors for various human diseases. This study aims to identify the prevalence of three SNPs of ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) in 235 unrelated individuals living in Thai Nguyen province, the northeast region of Vietnam. METHODS: The target genotypes were identified by using PCR direct sequencing, and their frequencies were compared to previous reports. RESULT: Our data showed that allele frequencies of ADH1B*2, ADH1C*2 and ALDH2*2 were 68.8%, 8.3% and 20.4%, respectively. The ADH1B*2 and ADH1C*2 frequencies were similar to those of the Kinh ethnic individuals living in the south region of Vietnam, while the ALDH2*2 frequency was higher. Compared to data from other countries, ADH1B*2 frequency is similar to the Philippines (60.5%) and Mongolia (62.9%) but significantly different from the other populations. The ADH1C*2 frequency is not so different compared to Japanese (5.7%) and Chinese (7.1%) but is quite different in other populations. ALDH2*2 frequency was lower than Japanese (29.3%), Indonesian (30%) and higher than other countries. Regarding the risk of alcoholism, the percentage of Vietnamese people in this study with genotypes related to alcohol dependence is 8.1%. In contrast, the carrier has genotypes protecting against alcoholism with high frequency, 91.9%. Among them, the individuals can cause high acetaldehyde accumulation accounting for 33.2%. CONCLUSION: This study helps to understand the genetic polymorphisms of alcohol metabolism genes in the community living in Thai Nguyen province, northeast of Vietnam, and provides valuable scientific data relating to alcohol consumption behavior as well as public health protection.

Severe loss of adipose tissue in a Vietnamese lipodystrophy patient caused by LMNA p.G465D mutation: a first clinical characterization and two-year follow-up.

OBJECTIVES: Familial partial lipodystrophy type 2 is the most well-known subtype of lipodystrophy. We describe for the first time the phenotype of a case with lipodystrophy, who carried heterozygous mutation c.G1394A (p.G465D) in the LMNA gene. CASE PRESENTATION: A 17-year-old girl was diagnosed with FPLD2 due to severe loss of subcutaneous fat in the extremities, buttocks and metabolic complications. However, there was no accumulation of fat over her face and neck, which is remarkably different from the FPLD2 clinical phenotypes. Two years of surveillance showed the challenge due to unable control of insulin resistance, glucose and lipid metabolism. Whole exome sequencing revealed the heterozygous mutation c.1394G>A at exon 11 of LMNA gene (p.G465D). CONCLUSIONS: Our case displayed an atypical phenotype of FPLD2 with metabolic anomalies, not cardiovascular diseases. The difficulties of medical management in this case pointed out the urgent need for more effective treatment for individuals suffering from this rare disease.

Novel mutations of the PAX6, FOXC1, and PITX2 genes cause abnormal development of the iris in Vietnamese individuals.

Purpose: Congenital iris abnormality is a feature of several genetic conditions, such as aniridia syndrome and anterior segment degeneration (ASD) disorders. Aniridia syndrome is caused by mutations in the PAX6 gene or its regulatory elements in the locus 11p13 or deletions of contiguous genes, while ASDs are the result of mutations in various genes, such as PAX6, FOXC1, PITX2, and CYP1B1. This study aims to identify pathogenic mutations in Vietnamese individuals with congenital anomalies of the iris. Methods: Genomic DNA was extracted from peripheral blood of 24 patients belonging to 15 unrelated families and their available family members. Multiplex ligation-dependent probe amplification (MLPA) was used to detect the deletions or duplications in the 11p13-14 region, including the PAX6 gene and its neighboring genes. Direct PCR sequencing was used to screen mutations in 13 exons and flanking sequences of the PAX6 gene. The patients without mutation in the PAX6 locus were further analyzed with whole exome sequencing (WES). Identified mutations were tested with segregation analysis in proband family members. Results: We identified a total of 8 novel and 4 recurrent mutations in 20 of 24 affected individuals from 12 families. Among these mutations, one large deletion of the whole PAX6 gene and another deletion of the PAX6 downstream region containing the DCDC1 and ELP4 genes were identified. Eight mutations were detected in PAX6, including four nonsense, three frameshift, and one splice site. In addition, two point mutations were identified in the FOXC1 and PITX2 genes in patients without mutation in PAX6. Some of the mutations segregated in an autosomal dominant pattern where family members were available. Conclusions: This study provides new data on causative mutations in individuals with abnormal development of iris tissue in Vietnam. These results contribute to clinical management and genetic counseling for affected people and their families.

Genome-wide analysis of SARS-CoV-2 strains circulating in Vietnam: Understanding the nature of the epidemic and role of the D614G mutation.

Genome-wide analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is essential to better understand infectivity and virulence and to track coronavirus disease 2019 (COVID-19) cases and outbreaks. We performed whole-genome sequencing of 27 SARS-CoV-2 strains isolated between January 2020 and April 2020. A total of 54 mutations in different genomic regions was found. The D614G mutation, first detected in March 2020, was identified in 18 strains and was more likely associated with a lower cycle threshold (<25) in real-time reverse-transcription polymerase chain reaction diagnostic tests than the original D614 (prevalence ratio = 2.75; 95% confidence interval, 1.19-6.38). The integration of sequencing and epidemiological data suggests that SARS-CoV-2 transmission in both quarantine areas and in the community in Vietnam occur at the beginning of the epidemic although the country implemented strict quarantine quite early, with strict contact tracing, and testing. These findings provide insights into the nature of the epidemic, as well as shape strategies for COVID-19 prevention and control in Vietnam.

Single Gold Bipyramid Nanoparticle Orientation Measured by Plasmon-Resonant Scattering Polarimetry.

The 3D orientation of a single gold nanoparticle is probed experimentally by light scattering polarimetry. We choose high-quality gold bipyramids (AuBPs) that support around 700 nm a well-defined narrow longitudinal localized surface plasmonic resonance (LSPR) which can be considered as a linear radiating dipole. A specific spectroscopic dark-field technique was used to control the collection angles of the scattered light. The in-plane as well as the out-of-plane angles are determined by analyzing the polarization of the scattered radiation. The data are compared with a previously developed model where the environment and the angular collection both play crucial roles. We show that most of the single AuBPs present an out-of-plane orientation consistent with their geometry. Finally, the fundamental role of the collection angles on the determination of the orientation is investigated for the first time. Several features are then deduced: we validate the choice of the analytical 1D model, an accurate 3D orientation is obtained, and the critical contribution of the evanescent waves is highlighted.

Characterization of envelope sequence of HIV virus in children infected with HIV in Vietnam.

BACKGROUND: HIV is characterized by high levels of genetic variability, including increased numbers of heterogeneous sequences of the envelope region. Therefore, studying genetic variability of HIV in relation to viral replication might facilitate prognosis of disease progression. METHODS: The study was designed as cross-sectional; data and samples of participants collected and analyzed env genes were obtained from 23 children enrolled by Vietnam National Children's Hospital. RESULTS: Substantial mutations in the C2 region were found in patients with high levels of viral replication while changes in the C3 region were mostly found in patients with low viral load. In the V1 region, we found profound amino acid modifications in patients with low HIV viral loads in contrast to the V2 sequence, where we identified single point mutations in patients with increased HIV viral load. The V3 region was relatively homogeneous, while profound deletions in the V4 region were detected in patients with increased viral replication. CONCLUSION: Our results suggest that genetic variations in different regions of the HIV envelope sequence, including both conserved C2 and C3 and variable V1/V2 and V4 regions, might be involved in increased viral infectivity and replication capacity. Such knowledge might help improve prediction of HIV progress and treatment in patients.

Prevalence of Opportunistic Infections and Associated Factors in HIV-Infected Men Who Have Sex With Men on Antiretroviral Therapy in Bach Mai Hospital, Hanoi, Vietnam: A Case-Control Study.

OBJECTIVE: To investigate the distribution of opportunistic infections (OIs) and factors associated with acquiring OIs in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) in comparison to those of heterosexual patients. METHOD: A cross-sectional study was conducted on 82 HIV-infected MSM and 120 HIV-infected heterosexual men in Bach Mai Hospital, Hanoi, Vietnam. Demographical characteristics and clinical data were collected and analyzed using appropriate statistics (Mann-Whitney, Chi-square, Fisher's exact test, and logistic regression). RESULTS: The prevalence of OIs among MSM and heterosexual patients were 63.4% and 81.7%, respectively. The most frequent OI in the MSM group was human papilloma virus (HPV) (11%), followed by hepatitis B virus (8.5%), mycobacterium tuberculosis (7.3%), and Talaromycosis (2.4%). CONCLUSIONS: Multivariate logistic regression analysis showed that buying sex (odds ratio (OR) = 4, 95% confidence interval (CI): 1.13-14.25) and injecting drugs (OR = 13.05, 95% CI: 2.39-71.21) were associated with increased odds of having OIs in heterosexual patients while increasing age (OR = 1.1, 95% CI: 1.01-1.24) was correlated to increased odd of acquiring OIs in the MSM group. HIV-infected MSM accumulates OIs with increasing age, while heterosexual individuals increase opportunistic infections by buying sex or injecting drugs.

Clinical features, isolation, and complete genome sequence of severe acute respiratory syndrome coronavirus 2 from the first two patients in Vietnam.

In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS-CoV-2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human-to-human transmission of SARS-CoV-2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi-morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies.

CYP2C19 genetic polymorphism in the Vietnamese population.

Background: Genetic polymorphism of CYP2C19 has been shown to affect enzyme activity and thereby contribute to inter-individual variability in drug metabolism and response. The complete genetic variation of CYP2C19 in Vietnam still remains obscure even though data of common alleles in Vietnamese Kinh have been reported.Aim: To establish the extent of CYP2C19 polymorphism in Vietnamese.Subjects and methods: The promoter and all nine exons of CYP2C19 in 100 healthy unrelated Vietnamese Kinh subjects were sequenced. Additionally, the CYP2C19 variants, *2, *3 and *17 were analysed by RFLP-PCR in 275 subjects of four minor ethnic groups in Vietnam (Tay, Muong, H'Mong and Nung).Results: In 100 Kinh subjects, the percentages of CYP2C19*1, CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles were 76%, 20.5%, 2.5% and 1%, respectively. Three novel variants in introns 2, 5 and 8 had no impact on mRNA splicing according to the Human Splicing Finder. The prevalence of CYP2C19*17 in Vietnamese Kinh was significantly lower compared with figures found in Western Asia and Europe, while CYP2C19*2 frequency was statistically higher than that in Western Asia and several countries in Europe. The frequency of CYP2C19*2 in Kinh was significantly lower than in the other four ethnic minorities.Conclusion: These results provide information on CYP2C19 polymorphism in the Vietnamese population, which could be useful for optimising drug therapies and precision medicine studies.

Single nucleotide and structural variants of CYP2D6 gene in Kinh Vietnamese population.

CYP2D6 genetic variations could result in alteration of CYP2D6 enzyme activity, leading to dissimilarity among individuals in regard of drug metabolism.This study aims to detect all genetic variants, allele, and genotype frequencies of CYP2D6 gene in 136 unrelated healthy Kinh Vietnamese volunteers. All single nucleotide variants (SNVs) and structural variations (SVs) of CYP2D6 gene were identified by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) assay.Totally, 30 SNVs and 9 SVs including a whole gene deletion, 8 hybrid structures, and tandem arrangements were identified. Of the 7 novel SNVs detected, the 3157G>T (R329L) substitution was predicted to be deleterious by PROVEAN; the 3851G>A (W358X) variant resulted in a truncated protein; and the 2988G>A variant located in the intron 6 was predicted to be capable of modifying splicing motif by Human Splicing Finder. We determined 29 different genotypes of CYP2D6 from 136 individuals. The most common alleles were the CYP2D6*10 (43.75%), *1 (18.75%), and tandem arrangement *36-*10 (12.13%).This study provides best information on CYP2D6 polymorphism comprising the newly discovered SNVs, structural variations, and their frequencies in Kinh Vietnamese. These new data would be valuable in view of precise dosing of CYP2D6 metabolized drugs and giving better treatment outcome.