METHODS: We utilised five GWAS (N=10 482) from Chinese (three cohorts, including one with type 2 diabetes and another one of children), Malay and Indian ethnic groups from Singapore. Data sets were analysed individually and subsequently in combined meta-analysis for Z-score body-mass index (BMI) associations.
RESULTS: Variants at the FTO locus showed the strongest associations with BMI Z-score after meta-analysis (P-values 1.16 × 10(-7)-7.95 × 10(-7)). We further detected associations with nine other index obesity variants close to the MC4R, GNPDA2, TMEM18, QPCTL/GIPR, BDNF, ETV5, MAP2K5/SKOR1, SEC16B and TNKS/MSRA loci (meta-analysis P-values ranging from 3.58 × 10(-4)-1.44 × 10(-2)). Three other single-nucleotide polymorphisms (SNPs) from CADM2, PTBP2 and FAIM2 were associated with BMI (P-value ≤ 0.0418) in at least one dataset. The neurotrophin/TRK pathway (P-value=0.029) was highlighted by pathway-based analysis of loci that had statistically significant associations among Singaporean populations.
CONCLUSION: Our data confirm the role of FTO in obesity predisposition among Chinese, Malays and Indians, the three major Asian ethnic groups. We additionally detected associations for 12 obesity-associated SNPs among Singaporeans. Thus, it is likely that Europeans and Asians share some of the genetic predisposition to obesity. Furthermore, the neurotrophin/TRK signalling may have a central role for common obesity among Asians.
METHODOLOGY/PRINCIPAL FINDINGS: Anopheles spp. were sampled using human landing catch (HLC) method at Paradason village in Kudat district of Sabah. The collected Anopheles were identified morphologically and then subjected to total DNA extraction and polymerase chain reaction (PCR) to detect Plasmodium parasites in the mosquitoes. Identification of Plasmodium spp. was confirmed by sequencing the SSU rRNA gene with species specific primers. MEGA4 software was then used to analyse the SSU rRNA sequences and bulid the phylogenetic tree for inferring the relationship between simian malaria parasites in Sabah. PCR results showed that only 1.61% (23/1,425) of the screened An. balabacensis were infected with one or two of the five simian Plasmodium spp. found in Sabah, viz. Plasmodium coatneyi, P. inui, P. fieldi, P. cynomolgi and P. knowlesi. Sequence analysis of SSU rRNA of Plasmodium isolates showed high percentage of identity within the same Plasmodium sp. group. The phylogenetic tree based on the consensus sequences of P. knowlesi showed 99.7%-100.0% nucleotide identity among the isolates from An. balabacensis, human patients and a long-tailed macaque from the same locality.
CONCLUSIONS/SIGNIFICANCE: This is the first study showing high molecular identity between the P. knowlesi isolates from An. balabacensis, human patients and a long-tailed macaque in Sabah. The other common simian Plasmodium spp. found in long-tailed macaques and also detected in An. balabacensis were P. coatneyi, P. inui, P. fieldi and P. cynomolgi. The high percentage identity of nucleotide sequences between the P. knowlesi isolates from the long-tailed macaque, An. balabacensis and human patients suggests a close genetic relationship between the parasites from these hosts.
SETTINGS AND DESIGN: Case-control study at Rheumatology Clinic of Universiti Sains Malaysia Hospital.
SUBJECTS AND METHODS: The sera of SLE patients and HCs were tested for the presence of anti-CLIC2 and anti-HMGB1 autoantibodies using human recombinant proteins and ELISA methodologies. Other serological parameters were evaluated according to routine procedures, and patients' demographic and clinical data were obtained.
STATISTICAL ANALYSIS: Mann-Whitney U-test, Chi-square test, Fisher's exact test, and receiver operating characteristic analysis.
RESULTS: Anti-CLIC2 autoantibody levels were significantly higher in SLE patients compared to HCs (P = 0.0035), whereas anti-HMGB1 autoantibody levels were not significantly elevated (P = 0.7702). Anti-CLIC2 and anti-HMGB1 autoantibody levels were not associated with ANA pattern, anti-dsDNA, and CRP. Interestingly, SLEDAI score (≥6) was associated with anti-CLIC2 (P = 0.0046) and with anti-HMGB1 (P = 0.0091) autoantibody levels.
CONCLUSION: Our findings support the potential of using anti-CLIC2 autoantibodies as a novel biomarker for SLE patients. Both anti-CLIC2 and anti-HMGB1 autoantibody levels demonstrated potential in monitoring SLE disease activity.
METHODS: We conducted a 1 to N case-control study involving 300 nasopharyngeal carcinoma (NPC) cases and 533 controls matched by age, gender and ethnicity to investigate the effect of hOGG1 Ser326Cys, ITGA2 C807T and XPD Lys751Gln polymorphisms on NPC risk. Linkage disequilibrium and haplotype analysis were conducted to explore the association of allele combinations with NPC risk. Restriction fragment length polymorphism (RFLP-PCR) was used for DNA genotyping.
RESULTS: No significant association was observed between hOGG1 Ser326Cys and ITGA2 C807T polymorphisms with NPC risk after adjustment for age, gender, ethnicity, cigarette smoking, alcohol and salted fish consumption. Lys/Lys genotype of XPD Lys751Gln polymorphism was associated with increased NPC risk (OR = 1.60, 95% CI = 1.06-2.43). Subjects with history of smoking (OR = 1.81, 95% CI = 1.26-2.60), and salted fish consumption before age of 10 (OR = 1.77, 95% CI = 1.30-2.42) were observed to have increased odds of NPC. The odds of developing NPC of CGC haplotype was significantly higher compared to reference AGC haplotype (OR = 2.20, 95% CI = 1.06-4.58).
CONCLUSION: The allele combination of CGC from hOGG1, ITGA2 and XPD polymorphisms was significantly associated with increased odds of NPC.
DESIGN: We used genome sequencing data to assess the prevalence of mutations in syndromic HH genes in an international cohort of patients with HH of unknown genetic cause.
PATIENTS: We undertook genome sequencing in 82 infants with HH without a clinical diagnosis of a known syndrome at referral for genetic testing.
MEASUREMENTS: Within this cohort, we searched for the genetic aetiologies causing 20 different syndromes where HH had been reported as a feature.
RESULTS: We identified a pathogenic KMT2D variant in a patient with HH diagnosed at birth, confirming a genetic diagnosis of Kabuki syndrome. Clinical data received following the identification of the mutation highlighted additional features consistent with the genetic diagnosis. Pathogenic variants were not identified in the remainder of the cohort.
CONCLUSIONS: Pathogenic variants in the syndromic HH genes are rare; thus, routine testing of these genes by molecular genetics laboratories is unlikely to be justified in patients without syndromic phenotypes.
METHODS: A total of 69 ticks were collected from 27 domestic fowl (Gallus gallus domesticus), 2 jungle fowl (Gallus gallus) and 3 Siamese firebacks (Lophura diardi) at 10 locations (provinces) in Thailand. Ticks were identified and PCR was used to amplify Coxiella bacteria 16S rRNA, groEL and rpoB genes from the extracted tick DNA. MEGA6 was used to construct phylogenetic trees via a Maximum Likelihood method.
RESULTS: The phylogenetic analysis based on the 16S rRNA gene showed that the Coxiella sequences detected in this study grouped in the same clade with Coxiella sequences from the same tick genus (or species) reported previously. In contrast, rpoB gene of the Coxiella bacteria detected in this study did not cluster together with the same tick genus reported previously. Instead, they clustered by geographical distribution (Thai cluster and Malaysian cluster). In addition, phylogenetic analysis of the groEL gene (the chaperonin family) showed that all Coxiella bacteria found in this study were grouped in the same clade (three sister groups).
CONCLUSIONS: To our knowledge, we found for the first time rpoB genes of Coxiella-like bacteria in Haemaphysalis wellingtoni ticks forming two distinct clades by phylogenetic analysis. This may be indicative of a horizontal gene transfer event.
METHODS: Characterization of the synthesized AuNPs was done by different techniques such as ultraviolet-visible spectrum absorption, X-ray diffraction, dynamic light scattering, Fourier transform infrared spectroscopy, transmission electron microscopy, and energy-dispersive X-ray analysis.
RESULTS: All the results showed the successful green synthesis of AuNPs from Sx, which induced apoptosis of C666-1 cell line (NPC cell line). There was a decline in both cell viability and colony formation in C666-1 cells upon treatment with Sx-AuNPs. The cell death was proved to be caused by autophagy and mitochondrial-dependent apoptotic pathway.
CONCLUSION: Thus, due to their anticancer potential, these nanoparticles coupled with Sx can be used for in vivo applications and clinical research in future.