PATIENTS AND METHODS: Materials and methods: The study included 128 patients with COPD and IHD, who were divided into two groups: group 1 included 72 patients with in¬frequent exacerbations of COPD (0-1 per year) and group 2 included 56 patients with frequent exacerbations of COPD (exacerbation of COPD ≥2 per year). The control groups consisted of 15 smokers without COPD and IHD, 11 practically healthy non-smokers and 11 patients with IHD who do not smoke. All patients underwent DNA isolation and purification, followed by determination of the Tyr113His polymorphism of the EPHX1 microsomal epoxide hydrolase gene (rs1051740).
RESULTS: Results: There was a significant association of the carriage of the CC genotype of the EPHX1 gene in patients with COPD and IHD (RO = 21.326 [95.0% CI 4.217-107.846], p <0.001) with a more severe course of COPD compared with the TT genotype of the EPHX1 gene.
CONCLUSION: Conclusions: Patients with COPD and coronary heart disease who were carriers of a homozygous variant СС of the EPHX1 gene have a reliable association with a more severe course of COPD with frequent exacerbations (higher class according to GOLD classification and more severe symptoms of COPD according to the СAT questionnaire).
METHODS: Studies published up to June 10, 2022, were searched in PubMed, Web of Science, Scopus, VIP, Wanfang, and China National Knowledge Infrastructure databases and screened for eligibility. Then, the combined odds ratio (OR) of the included studies was estimated based on five genetic models, i.e., homozygous (Met/Met vs. Thr/Thr), heterozygous (Thr/Met vs. Thr/Thr), dominant (Thr/Met + Met/Met vs. Thr/Thr), recessive (Met/Met vs. Thr/Thr + Thr/Met) and allele (Met vs. Thr). The study protocol was preregistered at PROSPERO (registration number: CRD42021235704).
RESULTS: Overall, our meta-analysis of 14 eligible studies involving 12,905 subjects showed that the p.Thr241Met polymorphism was significantly associated with increased glioma risk in both homozygous and recessive models (homozygous, OR = 1.381, 95% CI = 1.081-1.764, P = 0.010; recessive, OR = 1.305, 95% CI = 1.140-1.493, P<0.001). Subgroup analyses by ethnicity also revealed a statistically significant association under the two aforementioned genetic models, but only in the Asian population and not in Caucasians (P>0.05).
CONCLUSION: We demonstrated that the XRCC3 p.Thr241Met polymorphism is associated with an increased risk of glioma only in the homozygous and recessive models.
METHODS: We analysed 24 children under 12 years old, all of whom met the criteria provided by the World Health Organization, 2020 for MIS-C diagnosis, from the Paediatric COVID-19 Registry in Kuwait (PCR-Q8). Demographic and clinical data were collected from medical records, and exome sequencing was performed on the children and their parents to identify rare exonic variants. These variants were prioritized using two approaches: a candidate genes approach employing trio segregation analysis, and a candidate variants approach using a gene panel informed by previous studies on MIS-C-related genetic variants and datasets of differentially expressed genes in MIS-C patients.
RESULTS: The candidate genes approach identified 53 unique genes in 20 of the 24 probands, including DDX60 and TMEM154, which were also differentially expressed between MIS-C and control groups. The candidate variants approach identified 33 rare, predicted deleterious heterozygous variants across 19 unique genes in 19 of the 24 probands, including both previously described and novel candidate variants for MIS-C. Pathway analysis of the identified genes from both approaches revealed significant involvement in immune response, viral defence, and inflammatory pathways.
CONCLUSION: This study underscores the monogenic susceptibility to MIS-C, enhancing the evidence base through comprehensive genetic analysis. The findings highlight the critical role of genetic predispositions in MIS-C and suggest that further functional genomics work is necessary to explore the mechanistic contributions of these genes, facilitating the development of targeted diagnostic strategies.
RESULTS: In keeping with prior studies, CYP2D6*10 was found to be the most common defective allele. Nearly half of the (48.5%) participants were classified as intermediate and poor metabolizers. Linear regression analysis suggested that impaired CYP2D6 activity could be a predictor of anxiety and depression, consistent with the putative role of CYP2D6 in the synthesis of serotonin and dopamine, the mood-boosting neurotransmitters. We hope this brief report will prompt larger-scale studies to further elucidate the contribution of CYP2D6 to the genetic underpinnings of mental well-being.
METHODS: In-depth interviews with 28 Malaysian BRCA mutation carriers with a history of breast cancer were conducted in addition to observing their RRSO decision-making consultations in the clinic.
RESULTS: The decision-making considerations among the carriers were centered around the overarching theme of "Negotiating cancer risk and womanhood priorities," with the following themes: (1) risk perception, (2) self-preservation, (3) motherhood obligation, and (4) the preciousness of marriage. Cognitive knowledge of BRCA risk was often conceptualized based on personal and family history of cancer, personal beliefs, and faith. Many women reported fears that RRSO would affect them physically and emotionally, worrying about the post-surgical impact on their motherhood responsibilities. Nevertheless, some reported feeling obliged to choose RRSO for the sake of their children. For some, their husband's support and approval were critical, with emotional well-being and sexuality reportedly perceived as important to sustaining married life. Despite reporting hesitancy toward RRSO, women's decisions about choosing this option evolved as their priorities changed at different stages of life.
CONCLUSIONS: Recognizing during clinic encounters with Malaysian women that RRSO decision-making involves negotiating the likelihood of developing cancer with the societal priorities of being a woman, mother, and wife may serve to support their decision-making.
OBJECTIVE: This scoping review aimed to explore the literature on molecular genetics of obesity in Malaysia. Specifically, we sought to characterize existing studies, identify the genetic determinants of obesity, and assess their association with obesity predisposition in the population.
METHODS: This scoping review followed the methodology of the Joanna Briggs Institute and used the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist as its guiding framework. Searches were conducted using electronic databases such as PubMed, ScienceDirect, and Scopus, filtering for human studies published until March 2024. Eligible studies included peer-reviewed articles on the Malaysian population irrespective of age or sex. This review excluded review articles, book chapters, non-peer-reviewed conference proceedings, gray literature, and preclinical studies, and the reference lists of the retrieved studies were manually examined to ensure thorough inclusion. The articles were subjected to a 2-stage screening process (title/abstract and full text) conducted by 2 reviewers to assess eligibility. Eligible articles were then extracted following a data extraction framework and organized into a charting table. Only studies investigating the genetics of obesity in Malaysian populations were included.
RESULTS: As of March 2024, our extensive search strategy has yielded 572 records. After removing 153 duplicates, 419 records were screened by title and abstract, resulting in 47 selected for full-text review. Of these, 34 were chosen for data extraction and detailed analysis. These studies predominantly involved participants from major ethnic groups (Malay, Chinese, and Indian) recruited from local health centers and university communities. The articles primarily explored the relationship between specific gene variants and obesity or obesity-related health parameters. This ongoing research is expected to be completed with a comprehensive scoping review by April 2025.
CONCLUSIONS: This review provides valuable insights into the genetic determinants of obesity in Malaysia, despite limitations such as no quality appraisal being conducted for the included studies and the search strategy being restricted to selected databases, potentially omitting relevant studies. However, this review ensured reliability and reproducibility by adhering to the Joanna Briggs Institute and PRISMA-ScR guidelines. Ultimately, this study advances the understanding of local research and sets the foundation for future molecular genetic studies to improve obesity risk prediction and management in Malaysia's multiethnic population.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/60838.
METHODS: Electronic databases were searched for studies investigating IL-37 and SLE. Data on IL-37 levels, SLE Disease Activity Index (SLEDAI) score, genetic polymorphisms, and its therapeutic effects from pre-clinical studies were extracted.
RESULTS: Previous studies presented conflicting findings on IL-37 levels in SLE patients. Some reported positive correlations with disease activity, while others observed associations between lower IL-37 and increased activity. Genetic variations in the IL-37 gene linked to SLE susceptibility have been reported. Pre-clinical studies using engineered mesenchymal stem cells or direct IL-37 treatment showed promise in reducing disease severity in mouse models and cell cultures of SLE. The analysis of multiple studies reveals that IL-37 expression varies significantly across different SLE subtypes.
CONCLUSIONS: While a potential link exists between IL and 37 and disease activity, genetic predisposition, and therapeutic benefit, further research is needed. Future studies with standardized designs, larger and more diverse populations, and mechanistic investigations are crucial to determine the therapeutic potential of IL-37 for SLE. This review highlights the need for well-designed clinical trials to evaluate the safety and efficacy of IL-37 therapy in patients with SLE.
METHODS: We imputed the classical HLA alleles, amino acids, and haplotypes using the Immunochip genotyping data of 1260 RA cases (i.e., 530 Malays, 259 Chinese, 412 Indians, and 59 mixed ethnicities) and 1571 controls (i.e., 981 Malays, 205 Chinese, 297 Indians, and 87 mixed ethnicities) from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study. Stepwise logistic regression was performed to identify the independent genetic risk factors for RA within the HLA region.
RESULTS: We confirmed that the HLA-DRB1 amino acid at position 11 with valine residue conferred the strongest risk effect for ACPA-positive RA (OR = 4.26, 95% CI = 3.30-5.49, PGWAS = 7.22 × 10-29) in the Malays. Our study also revealed that HLA-DRB1 amino acid at position 96 with histidine residue was negatively associated with the risk of developing ACPA-positive RA in the Indians (OR = 0.48, 95% CI = 0.37-0.62, PGWAS = 2.58 × 10-08). Interestingly, we observed that HLA-DQB1*03:02 allele was inversely related to the risk of developing ACPA-positive RA in the Malays (OR = 0.17, 95% CI = 0.09-0.30, PGWAS = 1.60 × 10-09). No association was observed between the HLA variants and risk of developing ACPA-negative RA in any of the three major ethnic groups in Malaysia.
CONCLUSIONS: Our results demonstrate that the RA-associated genetic factors in the multi-ethnic Malaysian population are similar to those in the Caucasian population, despite significant differences in the genetic architecture of HLA region across populations. A novel and distinct independent association between the HLA-DQB1*03:02 allele and ACPA-positive RA was observed in the Malays. In common with the Caucasian population, there is little risk from HLA region for ACPA-negative RA.
METHODS: A systematic review and meta-analysis were performed of published studies from 1950 to 2010 using keyword searches in MEDLINE, EMBASE, EBM Reviews, and BIOSIS Previews.
RESULTS: In all, 477 abstracts were identified and data extracted from 93 studies, comprising 17,976 IBD patients and 27,350 age- and sex-matched controls. Major nucleotide oligomerization domain (NOD)-2 variants in Western Crohn's disease (CD) patients were not associated with CD in Han Chinese, Japanese, South Korean, Indian, and Malaysian populations. New NOD2 mutations were, however, associated with CD in Malaysians (JW1), Han Chinese, and Indians (P268S). Autophagy-related protein 16-linked 1 (ATG16L1) was not associated with CD in East Asians (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.84-1.13). Interleukin (IL)-23R was associated with CD in South Koreans (OR 1.8; 95% CI 1.16-2.82) and a single nucleotide polymorphism in IL-23R (Gly149Arg) was protective of CD in Han Chinese (OR 0.3; 95% CI 0.15-0.60). Tumor necrosis factor (TNF) superfamily gene-15 (SF15) polymorphisms were associated with CD (OR 2.68; 95% CI 1.86-3.86), while TNF-308 polymorphisms (OR 1.82; 95% CI 1.15-2.9), cytotoxic T lymphocyte antigen (CTLA)-4 (OR 2.75; 95% CI 1.22-6.22) and MICA allele (OR 2.41; 95% CI 1.89-3.07) were associated with ulcerative colitis in Asians.
CONCLUSIONS: Genetic mutations of IBD in Asians differ from Caucasians. New mutations and susceptibility genes identified in Asian IBD patients provide an opportunity to explore new disease-associated mechanisms in this population of rising incidence.
MATERIALS AND METHODS: We used 125 tumor samples from patients with a histologically confirmed diagnosis of renal cancer T1-4N0-1M0-1. A method described by Chomczynski and Sacchi was used to isolate nucleic acids. The mRNA levels were determined using a reverse transcription polymerase chain reaction and calculated according to ΔΔCt formula, taking into account the reaction efficiency.
RESULTS: mRNA of the FCGR3A gene was detected in all tumor tissue samples under study; in contrast, mRNA of the FCGR3B gene was found only in 92.0% (115/125) of cases. In tumors classified as pT1, the mRNA content of the FCGR3A gene was significantly lower than that in tumor samples of pT3 size. There was the significant increase in the mRNA content of both genes with an increase in tumor grade, as well as in the cases with distant metastases. The presence of a tumor thrombus in the inferior vena cava system was accompanied by a significant increase in the mRNA content of the FCGR3A gene.
CONCLUSION: In tumor tissue samples from patients with clear cell renal cancer, the predominant production of the FCGR3A mRNA was observed in comparison with the FCGR3B mRNA. The revealed relationship of an increased amount of the FCGR3A mRNA and, in some cases, the FCGR3B mRNA with a number of clinical and morphological factors enables to consider the mRNA level of the genes as new monitoring biomarkers.
METHODS: Mutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays.
RESULTS: PTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks.
CONCLUSION: Despite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.