Allopurinol-induced severe cutaneous adverse reactions in Vietnamese: the role of HLA alleles and other risk factors.

Aim: To reveal the association of three class I HLA alleles, including HLA-A*33:03, HLA-B*58:01 and HLA-C*03:02, and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese patients. Methods: A case-control study on 100 allopurinol-induced SCARs patients, 183 tolerant controls and 810 population controls was performed. The HLA-A*33:03 and HLA-C*03:02 alleles were detected with the nested allele-specific PCR method; the HLA-B*58:01 allele was detected with the sequence-specific primer PCR method. Results: There were strong associations between HLA-B*58:01 and HLA-C*03:02 and allopurinol-induced SCARs. Specific associations were found between HLA-B*58:01 and Stevens-Johnson syndrome/toxic epidermal necrolysis and between HLA-C*03:02 and drug reaction with eosinophilia and systemic symptoms, with a gene dosage effect. The multivariate regression analysis indicated two significant independent risk factors: HLA-B*58:01/HLA-C*03:02 and estimated glomerular filtration rate <60 ml/min/1.73 m2. The specificity, positive predictive value and negative predictive value of HLA-B*58:01 testing were higher than the HLA-C*03:02 or the multiplex testing, especially in patients with impaired renal function. Conclusion: The results supported pre-treatment HLA-B*58:01 testing in Vietnamese patients with declined renal function to prevent SCARs.

High incidence of type 2 diabetes in a population with normal range body mass index and individual prediction nomogram in Vietnam.

AIMS: The study aimed at determining 5-year incidence and prediction nomogram for new-onset type 2 diabetes (T2D) in a middle-aged population in Vietnam. METHODS: A population-based prospective study was designed to collect socio-economic, anthropometric, lifestyle and clinical data. Five-year T2D incidence was estimated and adjusted for age and sex. Hazard ratio (HR) for T2D was investigated using discrete-time proportional hazards model. T2D prediction model entering the most significant risk factors was developed using the multivariable logistic-regression algorithm. The corresponding prediction nomogram was constructed and checked for discrimination, calibration and clinical usefulness. RESULTS: The age- and sex-adjusted incidence was 21.0 cases (95% CI: 12.2-40.0) per 1000 person-years in people with mean BMI of 22.2 (95% CI: 21.9-22.7 kg/m2 ). The HRs (95% CI) for T2D were 1.14 (1.05-1.23) per 10 mmHg systolic blood pressure, 1.05 (1.03-1.08) per 1 cm waist circumference, 1.40 (1.13-1.73) per 1 mmol/L fasting blood glucose, 1.77 (1.15-2.71) per sleeping time (<6 h/day vs 6-7 h/day) and 2.12 (1.25-3.61) per residence (urban vs rural). The prediction nomogram for new-onset T2D had a good discrimination (area under curve: 0.711, 95% CI: 0.666-0.755) and fit calibration (mean absolute error: 0.009). For the predicted probability thresholds between 0.03 and 0.36, the nomogram showed a positive net benefit, without increasing the number of false positives. CONCLUSION: This study highlighted an alarmingly high incidence of T2D in a middle-aged population with a normal range BMI in Vietnam. The individual prediction nomogram with decision curve analysis for new-onset T2D would be valuable for early detection, intervention and treatment of the condition.

A novel nested allele-specific PCR protocol for the detection of the HLA-A*33:03, a SCAR-associated allele, in Vietnamese people.

BACKGROUND: Severe cutaneous adverse drug reactions (SCARs) are rare but deadly drug reactions with severe damages to patients. One of the most well-known SCARs risk factors is the human leukocyte antigen (HLA) genes polymorphism. Among the HLA polymorphic alleles, the HLA-A*33:03 allele has been found in association with SCARs induced by various drugs, especially in Asian people. There has not been any report on the specific detection protocol of the HLA-A*33:03 allele. OBJECTIVE: This study aimed to design a nested AS-PCR protocol for detecting and distinguishing diplotype genotype of the HLA-A*33:03 allele. METHODS: A nested allele-specific (AS)-PCR protocol with four primer sets was designed. The method was compared with the Sanger sequencing method on 100 samples of unknown genotypes of unrelated Vietnamese people. RESULTS: The nested AS-PCR method could identify the HLA-A*33:03 allele and the HLA-A*33:03 diplotype genotypes. Comparison with the Sanger sequencing method showed an absolute agreement (κ = 1.00, p < 0.001). The nested ASPCR protocol had a sensitivity of 100% (95%CI: 92.13-100%) and a specificity of 100% (95%CI: 93.51-100%). The protocol was used for the determination of HLA-A*33:03 allele distribution in 810 unrelated Vietnamese Kinh people, showing a frequency of HLA-A*33:03 carriers of 19.6% and an allele frequency of 10.55%. CONCLUSIONS: A novel nested AS-PCR method with a hundred-percent sensitivity and a specificity for the HLA-A*33:03 allele detection was reported. The protocol can be applied for the stratification of patients at SCAR risks with various drugs.

A Novel Allele-Specific PCR Protocol for the Detection of the HLA-C*03:02 Allele, a Pharmacogenetic Marker, in Vietnamese Kinh People.

BACKGROUND: Allopurinol, a common anti-hyperuricemia drug, is well known as an inducer of severe cutaneous adverse drug reactions (SCARs). One of the most well-defined risk factors of allopurinol-induced SCARs is the presence of polymorphic alleles of human leukocyte antigen (HLA) genes, such as HLA-B*58:01 and HLA-C*03:02 alleles. There is no commercial test or published in-house protocol for the specific detection of the HLA-C*03:02 allele. In this article, we established for the first time a simple allele-specific (AS) PCR method to identify HLA-C*03:02 allele carriers, and at the same time, determine their zygosities. METHODS: A two-step AS-PCR protocol, using four primer sets, was designed to specifically amplify and differentiate the HLA-C*03:02 allele from 17 other HLA-C alleles found in Vietnamese people. The protocol was validated with PCR-sequencing-based typing (SBT) of 100 samples of unknown genotypes. RESULTS: The PCR protocol can detect the HLA-C*03:02 allele and determine the zygosity. The results of this protocol were highly consistent with those of the SBT (ĸ = 0.98, p < 0.001). Regarding the specific detection of the HLA-C*03:02 allele, the PCR protocol had a sensitivity of 100% (95% CI: 91.61-100%) and specificity of 98.3% (95% CI: 90.9-99.7%). The protocol was used to determine the distribution of the HLA-C*03:02 allele in 810 unrelated Vietnamese Kinh people, 14.2% of which were HLA-C*03:02 carriers, the allele frequency was 7.5%. CONCLUSION: A novel AS-PCR protocol with a sensitivity of 100% for the detection of the HLA-C*03:02 allele was established. The protocol can be used for personalized treatment with allopurinol in order to minimize the risk of SCARs in Vietnamese people as well as in other Asian populations with similar genetic characteristics.

First Report on Multidrug-Resistant Methicillin-Resistant Staphylococcus aureus Isolates in Children Admitted to Tertiary Hospitals in Vietnam.

The extensive distribution of multidrug-resistant (MDR) methicillin-resistant Staphylococcus aureus (MRSA) poses a threat to healthcare worldwide. This study aimed to investigate the MDR and molecular patterns of MRSA isolates in children admitted to the two biggest tertiary care pediatric hospitals in northern and southern Vietnam. A total of 168 MRSA strains were collected to determine antibiotic susceptibility by minimum inhibitory concentration tests. Antibiotic-resistant genes, pulsed-field gel electrophoresis, staphylococcal cassette chromosome mec (SCCmec) typing, and multilocus sequence typing were used for the molecular characterization of MRSA. Among the total strains, the MDR rate (51.8%) was significantly higher in the northern hospital than in the southern hospital (73% vs. 39%, p < 0.0001). The MDR-MRSA with the highest rates were "ciprofloxacin-erythromycin-gentamicintetracyclines" (35.6%), followed by "erythromycin-tetracycline-chloramphenicol" (24.1%), and "ciprofloxacin-erythromycin-gentamicin" (19.5%), showing an accumulative total of 79.3%. The most susceptible antibiotics were rifampicin (100%) and vancomycin (100%), followed by doxycycline (94.0%), meropenem (78.0%), and cefotaxime (75.0%). The SCCmecII strains showed greater resistance to gentamicin, ciprofloxacin, tetracycline, meropenem and cephalosporins compared with the other strains. The SCCmecII strains exhibited the highest rate in the tested genes (aacA/aphD: 55.2%, ermA/B/C: 89.7%, and tetK/M: 82.8%). ST5- SCCmecII was the predominant clone in the northern hospital, whereas SCCmecIVa was more pronounced in the southern hospital. In conclusion, our results raised concerns about the predominant MDR-MRSA strains in the pediatric hospitals in Vietnam. The north-south difference in the antibiotic resistance patterns and genetic structure of MRSA suggests different MRSA origins and various uses of antimicrobial agents between the two regions.

Bifidobacterium species lower serum glucose, increase expressions of insulin signaling proteins, and improve adipokine profile in diabetic mice.

This study, using C57BL/6J mice with streptozotocin (STZ)-induced diabetes, aimed to determine whether Bifidobacterium species (spp.) both induces the expressions of proteins in the insulin signaling pathway and enhances the expressions of certain adipocytokines. The protein expressions of IκB kinase alpha (IKKα), IκB kinase beta (IKKß), nuclear factor-kappaB inhibitor alpha (IκBα), and the mitogen-activated protein kinase (MAPK) pathway were also investigated. Oral administration of Bifidobacterium spp. reduced blood glucose levels significantly and increased the protein expressions of insulin receptor beta, insulin receptor substrate 1, protein kinase B (Akt/PKB), IKKα, and IκBα. Extracellular-signal-regulated kinase 2 (ERK2) showed increased expression. Bifidobacterium spp. also induced the adiponectin expression and decreased both macrophage chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) expression. In addition, IKKß, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase expressions showed no significant changes in both groups. In conclusion, Bifidobacterium spp. may be the promising bacteria for treating diabetes.

Oral administration of Bifidobacterium spp. improves insulin resistance, induces adiponectin, and prevents inflammatory adipokine expressions.

The intestinal microbiome might be an important contributor to the development of type 2 diabetes. This study was designed to test the hypothesis that oral administration of Bifidobacterium species (spp.) (including B. longum, B. bifidum, B. infantis, and B. animalis) may both ameliorate insulin resistance and reduce the expressions of inflammatory adipocytokines. Male Swiss-Webster mice fed a high-fat diet with or without oral administration of Bifidobacterium spp. for 5 weeks were subjected to an insulin tolerance test and an oral glucose tolerance test. Plasma levels of glucose at 30, 60, 90 and 120 min after insulin injection or glucose administration were significantly lower in the Bifidobacterium spp. than in the control group (P < 0.05), showing the beneficial effect of oral administration on insulin resistance in obese Swiss mice. In addition, Bifidobacterium spp. increased the adiponectin mRNA level and decreased those of monocyte chemoattractant protein 1 and interleukin 6 in non-diabetic C57BL/6J mice fed a normal diet, indicating a molecular mechanism which may ameliorate the inflammatory state, thereby reducing insulin resistance. In conclusion, oral administration of Bifidobacterium spp. improves insulin resistance and glucose tolerance in obese mice by reducing inflammation, as it does in the lean state.

Pre-germinated brown rice reduced both blood glucose concentration and body weight in Vietnamese women with impaired glucose tolerance.

We have reported that newly diagnosed type 2 diabetes mellitus (DM) patients in Vietnam have a low body mass index (BMI) of around 23 and that the major factor for this is high white rice (WR) intake. Brown rice (BR) is known to be beneficial in the control of blood glucose levels; however, it has the property of unpleasant palatability. Pre-germinated brown rice (PGBR) is slightly germinated by soaking BR in water as this reduces the hardness of BR and makes it easier to eat. This study was designed to evaluate the effect of a 4-mo PGBR administration on various parameters in Vietnamese women aged 45-65 y with impaired glucose tolerance (IGT). Sixty subjects were divided into a WR or PGBR group. For the first 2 wk, WR was replaced by 50% PGBR, then for 2 wk by 75% PGBR and from the second month 100%. Before the beginning of the study and at the end of the study, 1) anthropometric measurements, 2) a nutrition survey for 3 nonconsecutive days by the 24 h recall method and 3) blood biochemical examinations were conducted. Fasting plasma concentrations of glucose and lipids and the obesity-related measurements and blood pressure were favorably improved only in the PGBR diet group. The present results suggest that replacing WR with PGBR for 4 mo may be useful in controlling body weight as well as blood glucose and lipid levels in Vietnamese women with IGT.