The Association of TOX3 Copy Number Variation with Gene Expression and Susceptibility to Nonsyndromic Cleft Lip and/or Palate in a Malay Cohort Nonsyndromic cleft lip and/or palate (NSCL/P) is a common congenital malformation with genetic influences. While Thymocyte selection-associated high mobility group box 3 (TOX3) is involved in other developmental processes, its role in NSCL/P remained unexplored. This study investigated the association between TOX3 copy number, expression, and NSCL/P in 64 Malay NSCL/P cases and 64 normal controls. Samples from patients undergoing cleft repair surgery and eligible volunteers for the control group were quantified via quantitative polymerase chain reactions (qPCR). A higher mean of TOX3 copy number was found in cases (2.195 ± 0.689) compared to controls (1.962 ± 0.558; p < 0.05). Similarly, a higher TOX3 expression was observed in cases (0.014 [IQR 0.024]) compared to controls (0.006 [IQR 0.019]; p < 0.001). Unadjusted analyses showed higher TOX3 copy number (OR = 1.850; p < 0.05) and its expression associated with NSCL/P. However, these associations were nullified after adjusting for sex and age (p > 0.05). Instead, male sex emerged as a significant independent predictor for NSCL/P (adjusted OR = 4.03; p < 0.001). Besides, an inverse, weak correlation was observed between TOX3 copy number and expression in NSCL/P patients (ρ = –0.285; p < 0.05) indicating the potential role of epigenetics in this condition. While male sex strongly contributed to the NSCL/P condition, our results suggest that TOX3 is not an independent genetic risk factor for NSCL/P in this population. These results highlight sex as a primary demographic risk factor and underscore the importance of considering demographic context in genetic association studies.

Introduction: Chronic lymphocytic leukaemia (CLL) is the most frequent adult leukaemia in the Western world. The clinical presentation varies greatly, from very indolent cases to those with aggressive and fast advancing disease. This variation has significant implications for clinical approaches, therapeutic tactics, and, ultimately, survival durations from diagnosis. Acquired chromosomal aberrations play a key role in CLL aetiology. Due to difficulty to obtain abnormal metaphases for analysis, few methods such as fluorescence in-situ hybridization (FISH) and multiplex ligation-dependent probe assay (MLPA) were employed to detect chromosomal aberration however the methods are limited to specific locus only. Thus, this study is aimed to detect the chromosomal aberrations using DNA microarray platform. Methods: In this retrospective study, DNA archive obtained from 7 CLL patients which collected at diagnosis and subjected to Affymetrix CytoScan® 750K single nucleotide polymorphism (SNP) array following the manufacture procedure. The raw data obtained were analysed using the Chromosome Analysis Suite (ChAS) software (Affymetrix) using annotations of genome version GRCh38 (hg38). Result: Out of 7 patients, 4 of them showing deletion of 13q while 3 of them showing deletion of 14q in various region . Some of the deleted loci were too small (0.42-0.6Mb) to be detected by conventional cytogenetic analysis (CCA). There was also the presence of additional chromosomal aberrations that could be missed by CCA, FISH, or MLPA due to cryptic deletion or duplication that was as small as 0.4MB in size. Conclusion: The present study showed that low resolution chromosomal aberration was able to be detected using DNA microarray platform in comparison to CCA, FISH and MLPA.

Introduction: C-reactive protein (CRP), urea, albumin, CRP/albumin ratio (CAR) and urea/albumin ratio (UAR) could be valuable biomarkers for determining the severity of illness in patients with COVID-19. This study aimed to determine the association between these markers and disease severity in COVID-19 patients on admission and days five to seven after admission. Methods: This retrospective study includes 153 adult COVID-19 patients admitted to Hospital Raja Perempuan Zainab II and Hospital Ampang from January 2021 to December 2021. Patients’ serum CRP, urea, albumin and creatinine levels were recorded on admission and on days five to seven after admission. The patients were categorised based on the Annex 2e guidelines published by the Ministry of Health, Malaysia and further classified as mild to moderate disease (stages 1-3) and severe to critical illness (stages 4-5). Results: On admission, urea, creatinine, CRP, UAR and CAR were significantly higher in the severe to critical group (p<0.001). The optimal cut-off value for the UAR was 0.16; the area under the curve (AUC) was 0.760, and sensitivity and specificity were 63.6% and 85.7%, respectively. The AUC of the CAR was 0.752, with 54.2% sensitivity and 91.4% specificity at an optimal cut-off value of 1.63. In severe to critical COVID-19 patients, albumin levels decreased significantly on days five to seven after admission, while urea levels remained significantly higher in this group (p<0.001, p<0.05, respectively). Conclusion: CRP, urea, albumin, CAR and UAR are promising biomarkers for predicting the severity of disease in COVID-19 patients.

Introduction: Imatinib mesylate has been widely used as a standard treatment for chronic myeloid leukemia (CML). It acts as a selective competitive inhibitor of the BCR-ABL tyrosine kinase. Despite the excellent efficacy on CML treatment, some patients developed resistance to the treatment. Mutation in the PDGFRA may be one of the factors involved in the mechanism of resistance that affects the response to imatinib. The mutational status of PDGFRA is highly relevant for prognosis and treatment prediction in CML patients. Thus, this study is intended to establish and validate a High Resolution Melting (HRM) analysis for PDGFRA exon 10 c.1432 T>C polymorphism in CML patients. Methods: High resolution melting (HRM) analysis was used to identify the c.1432 T > C polymorphism in PDGFRA exon 10 (n =86; response = 43; resistance = 43). The results from HRM analysis were compared and validated with Sanger sequencing. The association between the polymorphism and treatment response was assessed by statistical analysis using binomial logistic regression analysis. Results: HRM analyses showed two different melt curves. One curve followed the shape of the reference, homozygous wild type (TT) and the other curve showed a different melting profile than the reference with the TC genotype (heterozygous variant). The results revealed that heterozygous variant (TC) genotype showed a high risk of acquiring resistance with an OR of 3.795; 95% CI: 1.502-9.591, with a statistically significant association, p = 0.005. HRM analysis also showed 100% sensitivity and specificity in the detection of PDGFRA exon 10. Conclusion: The HRM analysis of PDGFRA exon 10 c.1432 T>C was successfully established. The exon 10 c.1432 T>C polymorphism shows a higher risk for the development of resistance toward imatinib treatment.

Introduction: Age-related macular degeneration (ARMD) is an ocular degenerative disorder that associated with impairment of central vision. Oxidative stress plays an important role in the pathogenesis of ARMD. The aim of this study was to determine the level of antioxidant enzymes (catalase and glutathione peroxidase) in tears among Malay ARMD patients. Methods: A cross sectional study was conducted between September 2015 and November 2017 among Malay ARMD patients. Schirmer paper was used to collect the tear samples. The level of catalase and glutathione peroxidase level in tears was evaluated using commercially available oxidative stress marker kits. Results: A total of 136 Malay ARMD patients were recruited into the study with 68 controls. Mean tear catalase and glutathione peroxidase levels were significantly lower in ARMD patients (1348.97 SD 109.11 µM and 453.87 SD 41.96 U/L respectively) as compared to the control group (1453.38 SD 38.87 µM and 502.28 SD 34.29 U/L respectively) (P<0.001 and P<0.001 respectively). Late ARMD has lower mean of catalase level in tears as compared to early ARMD (P=0.044). Based on subtypes of neovascular late ARMD, neovascular ARMD has lower mean catalase level in tears compared to idiopathic polypoidal choroidal vasculopathy (IPCV) (P=0.031). Conclusion: This study showed that antioxidant enzyme might play an important factor in the pathogenesis of ARMD.

Screening of the entire human genome using high-density single nucleotide polymorphism array (SNPA) has become a powerful technique used in cancer genetics and population genetics studies. The GeneChip® Mapping Array, introduced by Affymetrix, is one SNPA platform utilised for genotyping studies. This GeneChip system allows researchers to gain a comprehensive view of cancer biology on a single platform for the quantification of chromosomal amplifications, deletions, and loss of heterozygosity or for allelic imbalance studies. Importantly, this array analysis has the potential to reveal novel genetic findings involved in the multistep development of cancer. Given the importance of genetic factors in leukaemogenesis and the usefulness of screening the whole genome, SNPA analysis has been utilised in many studies to characterise genetic aberrations in childhood acute lymphoblastic leukaemia.