Leptin and interleukin-1ß levels associated with osteoarthritis in Vietnamese patients: a cross-sectional analysis.

Leptin and interleukin-1 beta (IL-1ß) are two extensively studied biomarkers associated with metabolic syndrome (MetS) and osteoarthritis (OA). Previous studies have mostly focused on either MetS or OA alone, with no available data on Vietnamese patients. This study aimed to investigate the levels of leptin and IL-1ß in this patient population and explore their association with clinical parameters of MetS and OA. The study included 164 patients with primary knee OA, who were classified into two categories based on the presence of MetS, and 78 healthy controls. The plasma leptin and IL-1ß levels were quantified by ELISA and correlated with clinical parameters. Leptin levels were higher in patients with OA (11.50±10.04 ng/mL) than in healthy controls (0.54±0.37 ng/mL) and increased in patients with MetS compared to those without MetS. IL-1ß levels were also significantly higher in OA patients (14.63±15.87 pg/mL) than in controls (7.79±5.11 pg/mL), but were not significantly different between the MetS and non-MetS groups. Leptin levels were positively correlated with body mass index, waist-to-hip ratio, visual analogue scale scores, HbA1c and insulin levels, and HOMA-IR index, whereas IL-1ß levels were only correlated with insulin levels and HOMA-IR index. ROC curve analysis revealed that leptin and IL-1ß levels could distinguish individuals with and without OA (AUC=0.96; 0.88, respectively), and individuals with and without MetS (AUC=0.82; 0.71, respectively). Our findings suggested that both leptin and IL-1ß levels were associated with both MetS and OA and may play a critical role in the pathogenesis of MetS-related OA.

Leptin and interleukin-1β levels associated with osteoarthritis in Vietnamese patients: a cross-sectional analysis

Leptin and interleukin-1 beta (IL-1β) are two extensively studied biomarkers associated with metabolic syndrome (MetS) and osteoarthritis (OA). Previous studies have mostly focused on either MetS or OA alone, with no available data on Vietnamese patients. This study aimed to investigate the levels of leptin and IL-1β in this patient population and explore their association with clinical parameters of MetS and OA. The study included 164 patients with primary knee OA, who were classified into two categories based on the presence of MetS, and 78 healthy controls. The plasma leptin and IL-1β levels were quantified by ELISA and correlated with clinical parameters. Leptin levels were higher in patients with OA (11.50±10.04 ng/mL) than in healthy controls (0.54±0.37 ng/mL) and increased in patients with MetS compared to those without MetS. IL-1β levels were also significantly higher in OA patients (14.63±15.87 pg/mL) than in controls (7.79±5.11 pg/mL), but were not significantly different between the MetS and non-MetS groups. Leptin levels were positively correlated with body mass index, waist-to-hip ratio, visual analogue scale scores, HbA1c and insulin levels, and HOMA-IR index, whereas IL-1β levels were only correlated with insulin levels and HOMA-IR index. ROC curve analysis revealed that leptin and IL-1β levels could distinguish individuals with and without OA (AUC=0.96; 0.88, respectively), and individuals with and without MetS (AUC=0.82; 0.71, respectively). Our findings suggested that both leptin and IL-1β levels were associated with both MetS and OA and may play a critical role in the pathogenesis of MetS-related OA.

Influence of the polymorphism of the DUSP14 gene on the expression of immune-related genes and development of pulmonary tuberculosis.

Recently, a genome-wide screening identified a functional single-nucleotide polymorphism in dual-specificity phosphatase 14 gene (DUSP14), which was associated with pulmonary tuberculosis (TB) in a West African study. DUSP14 regulates T-cell proliferation and cytokine production in a negative way via dephosphorylation and inactivation of key signaling molecules. The aim of this study is to further explore the possible significance of the DUSP14 polymorphism. Total RNA was extracted from the whole blood of 109 healthcare workers (HCWs) in Vietnam and subjected to quantitative reverse-transcription PCR for DUSP14 and 20 immune-related genes. DUSP14 rs1051838 was genotyped in 502 new pulmonary TB patients and 506 healthy controls. Among disease-free individuals (HCWs), T-helper type-1 (Th1)-related genes, interferon-gamma receptor 2 (IFNGR2) and signal transducer and activator of transcription-1 (STAT1) mRNA levels significantly increased as the number of A alleles of rs1051838 increased, whereas the DUSP14 mRNA level tended to decrease. The AA genotype was associated with protection against active TB in younger patients (⩽45 years old, OR=0.63, 95% CI 0.44-0.90). Our results suggest that a low-expression genotype of DUSP14 accompanied by high transcript levels of Th1 immune-related genes may confer protection against early TB development.

Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese.

The genetic basis for susceptibility to malaria has been studied widely in African populations but less is known of the contribution of specific genetic variants in Asian populations. We genotyped 67 single-nucleotide polymorphisms (SNPs) in 1030 severe malaria cases and 2840 controls from Vietnam. After data quality control, genotyping data of 956 cases and 2350 controls were analysed for 65 SNPs (3 gender confirmation, 62 positioned in/near 42 malarial candidate genes). A total of 14 SNPs were monomorphic and 2 (rs8078340 and rs33950507) were not in Hardy-Weinberg equilibrium in controls (P<0.01). In all, 7/46 SNPs in 6 genes (ICAM1, IL1A, IL17RC, IL13, LTA and TNF) were associated with severe malaria, with 3/7 SNPs in the TNF/LTA region. Genotype-phenotype correlations between SNPs and clinical parameters revealed that genotypes of rs708567 (IL17RC) correlate with parasitemia (P=0.028, r(2)=0.0086), with GG homozygotes having the lowest parasite burden. Additionally, rs708567 GG homozygotes had a decreased risk of severe malaria (P=0.007, OR=0.78 (95% CI; 0.65-0.93)) and death (P=0.028, OR=0.58 (95% CI; 0.37-0.93)) than those with AA and AG genotypes. In summary, variants in six genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese. Further replicative studies in independent populations will be necessary to confirm these findings.

Association of TLR polymorphisms with development of tuberculosis in Indonesian females.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is a major cause of morbidity and mortality worldwide. Many candidate genes have been investigated for a possible association with TB. Toll-like receptors (TLRs) are known to play important roles in human innate immune systems. Polymorphisms in and functions of TLRs have been investigated to identify associations with specific infectious diseases, including TB. Here, we examined whether single-nucleotide polymorphisms (SNPs) in TLRs and genes in TLR signaling were associated with TB susceptibility in Indonesian and Vietnamese populations. A statistically significant association was observed between TB susceptibility in a classified Indonesian female group and rs352139, an SNP located in the intron of TLR9, using the genotype (P = 2.76E-04) and recessive (AA vs AG+GG, P = 2.48E-04, odds ratio = 1.827, 95% confidence interval = 1.321-2.526) models. Meta-analysis of the Indonesian and Vietnamese populations showed that rs352139 was significantly associated with TB in the recessive model. This finding indicated that a TLR9 polymorphism might have an important role in the susceptibility to M. tuberculosis in Asian populations.

HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in the Kinh population in Vietnam.

Allele and haplotype frequencies of the human leukocyte antigens (HLA) were studied in the Kinh Vietnamese population. We analyzed 170 unrelated healthy individuals. DNA-based HLA typing was performed using a microsphere-based array genotyping platform with sequence-specific oligonucleotide probes to distinguish HLA-A, -B, -C, -DRB1 and -DQB1 alleles. A total of 21 HLA-A, 37 HLA-B, 18 HLA-C, 25 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. HLA-A*1101, A*2402, A*3303, B*1502, B*4601, Cw*0102, Cw*0702, Cw*0801, DRB1*1202, DQB1*0301, DQB1*0303, and DQB1*0501 were found with frequencies higher than 10%. Two representative haplotypes bearing two to five HLA loci were A*1101-B*1502 and A*3303-B*5801 for HLA-A-B; Cw*0801-B*1502 and Cw*0102-B*4601 for HLA-C-B; B*1502-DRB1*1202 and B*4601-DRB1*0901 for HLA-B-DRB1; DRB1*1202-DQB1*0301 and DRB1*0901-DQB1*0303 for HLA-DRB1-DQB1; A*1101-Cw*0801-B*1502 and A*3303-Cw*0302-B*5801 for HLA-A-C-B; A*1101-B*1502-DRB1*1202 and A*2901-B*0705-DRB1*1001 for HLA-A-B-DRB1, A*1101-Cw*0801-B*1502-DRB1*1202-DQB1*0301 and A*2901-Cw*1505-B*0705-DRB1*1001-DQB1*0501 for HLA-A-C-B-DRB1-DQB1. Allele distribution and haplotype analysis demonstrated that the Vietnamese population shares HLA patterns with southern Chinese, Thai, Javanese and Micronesians, while it also retains unique characteristics.

Treatment of falciparum malaria in Vietnamese children: the need for combination therapy and optimized dosage regimens.

To assess the in vivo sensitivity of Plasmodium falciparum to mefloquine and artesunate in a hyperendemic area of southern Viet Nam, we studied 41 children and 21 adults from a remote commune who had uncomplicated falciparum malaria without previous treatment. Patients were randomly allocated to artesunate (4 mg/kg on day 0 and 2 mg/kg on days 1-4) or mefloquine (10 mg/kg followed by 5 mg/kg at 6 h). Serial assessments were performed over 28 days. Of 31 patients allocated artesunate, nine (29%) redeveloped parasitaemia during follow-up compared with 23% (seven of 30) who received mefloquine. Of the 41 children, 15 (37%) had recrudescence/re-infection compared with only one of 20 adults (5%; p < 0.001). Significantly more children than adults failed on mefloquine treatment (37% vs 0%; p = 0.021) and one case showed RIII resistance. There was no significant difference in the case of artesunate. In regression analysis, parasitaemia was an independent predictor of recrudescence/re-infection after mefloquine (p = 0.02). These data support the use of combination therapy such as artesunate plus mefloquine for falciparum malaria in a hyperendemic area of Viet Nam. Primarily because of their greater parasite densities, children should be given higher doses of mefloquine (e.g. 25 mg/kg).

Withanolide glycosides from Dunalia australis.

Four new withanolide glycosides, (20R,22R)-O-(3)-[beta-D- xylopyranosyl(1----3), beta-D-xylopyranosyl(1----4)]-beta-D-glucopyranosyl-3 beta,20-dihydroxy-1 alpha-acetoxy-witha-5,24-dienolide, (20R,22R)-O-(3)-[beta-D-xylopyranosyl(1----3), beta-D-glucopyranosyl(1----4)]-beta-D-glucopyranosyl-3 beta,20-dihydroxy-1 alpha-acetoxy-witha-5,24-dienolide, (20R,22R)-O-(3)-[beta-D- glucopyranosyl(1----3), beta-D-glucopyranosyl(1----4)]-beta-D-glucopyranosyl- 3 beta,20-dihydroxy-1 alpha-acetoxy-witha-5,24-dienolide and (20R,22R)-O-(3)-[beta-D-glucopyranosyl(1----3), beta-D- glucopyranosyl(1----4)]-beta-D-glucopyranosyl-3 beta, 12 beta,20-trihydroxy- 1 alpha,acetoxy-witha-5,24-dienolide, named dunawithanines C, D, E and F, respectively, were isolated from Dunalia australis. Their structures were elucidated on the basis of spectral and chemical evidence, especially NMR data of the peracetates.