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Fulltext Deep Small RNA Sequencing of BRAF V600E Mutated Papillary Thyroid Carcinoma With Lymph Node Metastasis

Yusof AM, Jamal R, Saidin S, Muhammad R, Suhaimi SNA, Rose IM, et al.

Front Genet, 2019;10:941.
PMID: 31649724 DOI: 10.3389/fgene.2019.00941
Fulltext Deep Transcriptome Sequencing of Pediatric Acute Myeloid Leukemia Patients at Diagnosis, Remission and Relapse: Experience in 3 Malaysian Children in a Single Center Study

Osman SH, Abu N, Aziz H, Chow YP, Wan Mohamad Nazarie WF, Ab Mutalib NS, et al.

Front Genet, 2020;11:66.
PMID: 32174960 DOI: 10.3389/fgene.2020.00066
Colorectal screening using the immunochemical faecal occult blood test kit among the Malaysian cohort participants

Abdullah N, Abd Jalal N, Ismail N, Kamaruddin MA, Abd Mutalib NS, Alias MR, et al.

Cancer Epidemiol, 2020 04;65:101656.
PMID: 31923638 DOI: 10.1016/j.canep.2019.101656

BACKGROUND: There has been a rapid increase in colorectal cancer (CRC) cases in Asian countries, including Malaysia. CRC is usually diagnosed at a late stage, and early detection of CRC is vital in improving survival. This study was conducted to determine the uptake rate of the immunochemical faecal occult blood test (iFOBT), the response rate to colonoscopy, and the CRC detection rate. We also wanted to identify the association between colorectal neoplasia and the Asia Pacific Colorectal Cancer Screening (APCS) scoring system.
METHODS: We recruited 2264 individuals from The Malaysian Cohort participants aged 35-65 years who consented to colorectal screening using the iFOBT kit from July 2017 until January 2019.
RESULTS: The response rate and positive iFOBT test rate of this study were 79.6% and 13.1% respectively. Among those with positive results, 125 individuals (52.7%) underwent colonoscopy; CRC was detected in six of them while 45 others (36.0%) had polyps. The overall CRC detection rate was 0.3% while the colorectal neoplasia detection rate (both colorectal cancer and colorectal polyps) was 2.3%. The APCS scoring indicated a significant association with colorectal neoplasia risk, with increasing trend by severity from moderate to high risk (3.46-11.14) compared to low risk. Most of the participants who were positive for iFOBT were those at high risk.
CONCLUSIONS: The awareness of CRC risk and iFOBT screening are important strategies for early detection of CRC. We showed a CRC detection rate of 0.3 % among those who volunteered to have the iFOBT screening.
Gene-environment interaction in chronic kidney disease among people with type 2 diabetes from The Malaysian Cohort project: a case-control study

Ahmad N, Shah SA, Abdul Gafor AH, Abdul Murad NA, Kamaruddin MA, Abd Jalal N, et al.

Diabet Med, 2020 11;37(11):1890-1901.
PMID: 32012348 DOI: 10.1111/dme.14257

AIM: To examine the possible gene-environment interactions between 32 single nucleotide polymorphisms and environmental factors that could modify the probability of chronic kidney disease.
METHODS: A case-control study was conducted involving 600 people with type 2 diabetes (300 chronic kidney disease cases, 300 controls) who participated in The Malaysian Cohort project. Retrospective subanalysis was performed on the chronic kidney disease cases to assess chronic kidney disease progression from the recruitment phase. We genotyped 32 single nucleotide polymorphisms using mass spectrometry. The probability of chronic kidney disease and predicted rate of newly detected chronic kidney disease progression were estimated from the significant gene-environment interaction analyses.
RESULTS: Four single nucleotide polymorphisms (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and five environmental factors (age, sex, smoking, waist circumference and HDL) were significantly associated with chronic kidney disease. Gene-environment interaction analyses revealed significant probabilities of chronic kidney disease for sex (PPARGC1A rs8192678), smoking (eNOS rs2070744, PPARGC1A rs8192678 and KCNQ1 rs2237895), waist circumference (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and HDL (eNOS rs2070744 and PPARGC1A rs8192678). Subanalysis indicated that the rate of newly detected chronic kidney disease progression was 133 cases per 1000 person-years (95% CI: 115, 153), with a mean follow-up period of 4.78 (SD 0.73) years. There was a significant predicted rate of newly detected chronic kidney disease progression in gene-environment interactions between KCNQ1 rs2283228 and two environmental factors (sex and BMI).
CONCLUSIONS: Our findings suggest that the gene-environment interactions of eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228 with specific environmental factors could modify the probability for chronic kidney disease.
Characterizing the genetic risk for type 2 diabetes in a Malaysian multi-ethnic cohort

Abdullah N, Abdul Murad NA, Attia J, Oldmeadow C, Mohd Haniff EA, Syafruddin SE, et al.

Diabet Med, 2015 Oct;32(10):1377-84.
PMID: 25711284 DOI: 10.1111/dme.12735

AIMS: To characterize the association with Type 2 diabetes of known Type 2 diabetes risk variants in people in Malaysia of Malay, Chinese and Indian ancestry who participated in the Malaysian Cohort project.
METHODS: We genotyped 1604 people of Malay ancestry (722 cases, 882 controls), 1654 of Chinese ancestry (819 cases, 835 controls) and 1728 of Indian ancestry (851 cases, 877 controls). First, 62 candidate single-nucleotide polymorphisms previously associated with Type 2 diabetes were assessed for association via logistic regression within ancestral groups and then across ancestral groups using a meta-analysis. Second, estimated odds ratios were assessed for excess directional concordance with previously studied populations. Third, a genetic risk score aggregating allele dosage across the candidate single-nucleotide polymorphisms was tested for association within and across ancestral groups.
RESULTS: After Bonferroni correction, seven individual single-nucleotide polymorphisms were associated with Type 2 diabetes in the combined Malaysian sample. We observed a highly significant excess in concordance of effect directions between Malaysian and previously studied populations. The genetic risk score was strongly associated with Type 2 diabetes in all Malaysian groups, explaining from 1.0 to 1.7% of total Type 2 diabetes risk variance.
CONCLUSION: This study suggests there is substantial overlap of the genetic risk alleles underlying Type 2 diabetes in Malaysian and other populations.
Study name: The Malaysian Cohort (TMC) project
Fulltext Participants Attrition in a Longitudinal Study: The Malaysian Cohort Study Experience

Abdullah N, Kamaruddin MA, Goh YX, Othman R, Dauni A, Jalal NA, et al.

Int J Environ Res Public Health, 2021 07 06;18(14).
PMID: 34299667 DOI: 10.3390/ijerph18147216

The attrition rate of longitudinal study participation remains a challenge. To date, the Malaysian Cohort (TMC) study follow-up rate was only 42.7%. This study objective is to identify the cause of attrition among TMC participants and the measures to curb it. A total of 19,343 TMC participants from Kuala Lumpur and Selangor that was due for follow-up were studied. The two most common attrition reasons are undergoing medical treatment at another government or private health center (7.0%) and loss of interest in participating in the TMC project (5.1%). Those who were inclined to drop out were mostly Chinese, aged 50 years and above, unemployed, and had comorbidities during the baseline recruitment. We have also contacted 2183 participants for the home recruitment follow-up, and about 10.9% agreed to join. Home recruitment slightly improved the overall follow-up rate from 42.7% to 43.5% during the three-month study period.
Study name: The Malaysian Cohort (TMC) project
Fulltext Development and Relative Validity of a Semiquantitative Food Frequency Questionnaire to Estimate Dietary Intake among a Multi-Ethnic Population in the Malaysian Cohort Project

Shahar S, Shahril MR, Abdullah N, Borhanuddin B, Kamaruddin MA, Yusuf NAM, et al.

Nutrients, 2021 Apr 01;13(4).
PMID: 33915922 DOI: 10.3390/nu13041163

Measuring dietary intakes in a multi-ethnic and multicultural setting, such as Malaysia, remains a challenge due to its diversity. This study aims to develop and evaluate the relative validity of an interviewer-administered food frequency questionnaire (FFQ) in assessing the habitual dietary exposure of The Malaysian Cohort (TMC) participants. We developed a nutrient database (with 203 items) based on various food consumption tables, and 803 participants were involved in this study. The output of the FFQ was then validated against three-day 24-h dietary recalls (n = 64). We assessed the relative validity and its agreement using various methods, such as Spearman's correlation, weighed Kappa, intraclass correlation coefficient (ICC), and Bland-Altman analysis. Spearman's correlation coefficient ranged from 0.24 (vitamin C) to 0.46 (carbohydrate), and almost all nutrients had correlation coefficients above 0.3, except for vitamin C and sodium. Intraclass correlation coefficients ranged from -0.01 (calcium) to 0.59 (carbohydrates), and weighted Kappa exceeded 0.4 for 50% of nutrients. In short, TMC's FFQ appears to have good relative validity for the assessment of nutrient intake among its participants, as compared to the three-day 24-h dietary recalls. However, estimates for iron, vitamin A, and vitamin C should be interpreted with caution.
Study name: The Malaysian Cohort (TMC) project
Prevalence of anaemia and associated risk factors amongst The Malaysian Cohort participants

Abdullah N, Ismail N, Abd Jalal N, Mohd Radin F, Othman R, Kamalul Arifin AS, et al.

Ann Hematol, 2020 Nov;99(11):2521-2527.
PMID: 32975589 DOI: 10.1007/s00277-020-04279-w

This study was aimed at determining the prevalence of anaemia amongst the Malaysian Cohort participants and the associated risk factors. This was a cross-sectional study that involved 102,388 participants from The Malaysian Cohort (TMC) aged between 35 and 70 years old recruited from April 2006 to September 2012. Venous blood was taken for the full blood count. The prevalence of anaemia was 13.8% with majority having the microcytic-hypochromic type (59.7%). Comparison between the ethnic groups showed that Indians have the highest prevalence of anaemia (19.9%), followed by Malays (13.1%), and Chinese (12.0%). The prevalence of anaemia was substantially higher in females (20.1%) compared to males (4.9%). Amongst the female participants, the prevalence of anaemia was highest amongst those who were younger than 49 years old and decreased as the age increased. In contrast, the prevalence of anaemia in males increased with age. Gender, ethnicity, age, marital status, presence of platelet disorders and kidney disease were significant risk factors associated with anaemia and contributed to 14.9% of the risk of developing anaemia in this population. The prevalence of anaemia amongst the Malaysian Cohort participants is 13.8% with the majority having the microcytic and hypochromic type implying iron deficiency as the main cause. It is important that those who have anaemia be further investigated and treated.
Study name: The Malaysian Cohort (TMC) project
Fulltext Utilization of complementary and alternative medicine in multiethnic population: The Malaysian Cohort Study

Abdullah N, Borhanuddin B, Patah AEA, Abdullah MS, Dauni A, Kamaruddin MA, et al.

J Evid Based Integr Med, 2018 4 14;23:2515690X18765945.
PMID: 29651870 DOI: 10.1177/2515690X18765945

BACKGROUND: This study aimed to identify the factors of CAM usage for general health and to determine the factors associated with the usage of different types of CAM after the diagnosis of chronic diseases among The Malaysian Cohort participants.
METHODS: This was a cross-sectional study derived from The Malaysian Cohort (TMC) project, a prospective population-based cohort aged between 35 to 65 years old that recruited from April 2006 to September 2012. Association between the CAM usage and contributing factors were determined via logistic regression.
RESULTS: The sample were mostly female (58.1%), Malays (43.1%), came from urban (71.9%), aged 44 years and below (26.8%) and had secondary education (45.9%). The prevalence of CAM usage varied across diseases; 62.8% in cancer patients, 53.3% in hypercholesterolemia, 49.4% in hypertensives and 48.6% in diabetics. General CAM usage was greater among female (OR: 1.54, 95% CI: 1.49, 1.59), Chinese (OR: 1.15, 95% CI: 1.12, 1.19), those with higher education (OR: 3.12, 95% CI: 3.00, 3.25), urban residents (OR: 1.55, 95% CI: 1.50, 1.61) and older people (OR ranging from 1.15 to 1.75) while for post-diagnosis of chronic diseases usage, the odds were higher among those with lower education and living in rural areas.
CONCLUSION: Health status, educational level, age, living location and types of chronic diseases were significant factors that influence CAM usage for the intent of either health maintenance or disease treatment. Further exploration on CAM safety and benefit are crucial to minimize the adverse effect and to ensure the efficacy of CAM product.
Study name: The Malaysian Cohort (TMC) project
Effects of simulated microgravity on gene expression and biological phenotypes of a single generation Caenorhabditis elegans cultured on 2 different media

Tee LF, Neoh HM, Then SM, Murad NA, Asillam MF, Hashim MH, et al.

Life Sci Space Res (Amst), 2017 Nov;15:11-17.
PMID: 29198309 DOI: 10.1016/j.lssr.2017.06.002

Studies of multigenerational Caenorhabditis elegans exposed to long-term spaceflight have revealed expression changes of genes involved in longevity, DNA repair, and locomotion. However, results from spaceflight experiments are difficult to reproduce as space missions are costly and opportunities are rather limited for researchers. In addition, multigenerational cultures of C. elegans used in previous studies contribute to mixture of gene expression profiles from both larvae and adult worms, which were recently reported to be different. Usage of different culture media during microgravity simulation experiments might also give rise to differences in the gene expression and biological phenotypes of the worms. In this study, we investigated the effects of simulated microgravity on the gene expression and biological phenotype profiles of a single generation of C. elegans worms cultured on 2 different culture media. A desktop Random Positioning Machine (RPM) was used to simulate microgravity on the worms for approximately 52 to 54 h. Gene expression profile was analysed using the Affymetrix GeneChip® C. elegans 1.0 ST Array. Only one gene (R01H2.2) was found to be downregulated in nematode growth medium (NGM)-cultured worms exposed to simulated microgravity. On the other hand, eight genes were differentially expressed for C. elegans Maintenance Medium (CeMM)-cultured worms in microgravity; six were upregulated, while two were downregulated. Five of the upregulated genes (C07E3.15, C34H3.21, C32D5.16, F35H8.9 and C34F11.17) encode non-coding RNAs. In terms of biological phenotype, we observed that microgravity-simulated worms experienced minimal changes in terms of lifespan, locomotion and reproductive capabilities in comparison with the ground controls. Taking it all together, simulated microgravity on a single generation of C. elegans did not confer major changes to their gene expression and biological phenotype. Nevertheless, exposure of the worms to microgravity lead to higher expression of non-coding RNA genes, which may play an epigenetic role in the worms during longer terms of microgravity exposure.
Fulltext Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family

Chow YP, Abdul Murad NA, Mohd Rani Z, Khoo JS, Chong PS, Wu LL, et al.

Orphanet J Rare Dis, 2017 Feb 21;12(1):40.
PMID: 28222800 DOI: 10.1186/s13023-017-0575-7

BACKGROUND: Pendred syndrome (PDS, MIM #274600) is an autosomal recessive disorder characterized by congenital sensorineural hearing loss and goiter. In this study, we describing the possible PDS causal mutations in a Malaysian family with 2 daughters diagnosed with bilateral hearing loss and hypothyroidism.
METHODS AND RESULTS: Whole exome sequencing was performed on 2 sisters with PDS and their unaffected parents. Our results showed that both sisters inherited monoallelic mutations in the 2 known PDS genes, SLC26A4 (ENST00000265715:c.1343C > T, p.Ser448Leu) and GJB2 (ENST00000382844:c.368C > A, p.Thr123Asn) from their father, as well as another deafness-related gene, SCARB2 (ENST00000264896:c.914C > T, p.Thr305Met) from their mother. We postulated that these three heterozygous mutations in combination may be causative to deafness, and warrants further investigation. Furthermore, we also identified a compound heterozygosity involving the DUOX2 gene (ENST00000603300:c.1588A > T:p.Lys530* and c.3329G > A:p.Arg1110Gln) in both sisters which are inherited from both parents and may be correlated with early onset of goiter. All the candidate mutations were predicted deleterious by in silico tools.
CONCLUSIONS: In summary, we proposed that PDS in this family could be a polygenic disorder which possibly arises from a combination of heterozygous mutations in SLC26A4, GJB2 and SCARB2 which associated with deafness, as well as compound heterozygous DUOX2 mutations which associated with thyroid dysfunction.
Fulltext Differing Contributions of Classical Risk Factors to Type 2 Diabetes in Multi-Ethnic Malaysian Populations

Abdullah N, Murad NAA, Attia J, Oldmeadow C, Kamaruddin MA, Jalal NA, et al.

Int J Environ Res Public Health, 2018 Dec 10;15(12).
PMID: 30544761 DOI: 10.3390/ijerph15122813

The prevalence of type 2 diabetes is escalating rapidly in Asian countries, with the rapid increase likely attributable to a combination of genetic and lifestyle factors. Recent research suggests that common genetic risk variants contribute minimally to the rapidly rising prevalence. Rather, recent changes in dietary patterns and physical activity may be more important. This nested case-control study assessed the association and predictive utility of type 2 diabetes lifestyle risk factors in participants from Malaysia, an understudied Asian population with comparatively high disease prevalence. The study sample comprised 4077 participants from The Malaysian Cohort project and included sub-samples from the three major ancestral groups: Malay (n = 1323), Chinese (n = 1344) and Indian (n = 1410). Association of lifestyle factors with type 2 diabetes was assessed within and across ancestral groups using logistic regression. Predictive utility was quantified and compared between groups using the Area Under the Receiver-Operating Characteristic Curve (AUC). In predictive models including age, gender, waist-to-hip ratio, physical activity, location, family history of diabetes and average sleep duration, the AUC ranged from 0.76 to 0.85 across groups and was significantly higher in Chinese than Malays or Indians, likely reflecting anthropometric differences. This study suggests that obesity, advancing age, a family history of diabetes and living in a rural area are important drivers of the escalating prevalence of type 2 diabetes in Malaysia.
Fulltext Targeted Next-Generation Sequencing Identifies Actionable Targets in Estrogen Receptor Positive and Estrogen Receptor Negative Endometriod Endometrial Cancer

Suhaimi SS, Ab Mutalib NS, Khor SS, Zain RRM, Syafruddin SE, Abu N, et al.

Front Pharmacol, 2018;9:750.
PMID: 30057548 DOI: 10.3389/fphar.2018.00750

Endometrioid endometrial cancer (EEC) is the commonest form of endometrial cancer and can be divided into estrogen receptor (ER) positive and negative subtypes. The mutational profiles of EEC have been shown to aid in tailoring treatment; however, little is known about the differences between the gene mutation profiles between these two subtypes. This study aims to investigate the gene mutation profile in ER positive and negative EEC, and to further elucidate the role of WHSC1 mutations in this cancer. EEC and normal endometrial tissues were obtained from 29 patients and subjected to next-generation sequencing (NGS) using Ion Ampliseq Comprehensive Cancer PanelTM targeting 409 cancer related. A total of 741 non-synonymous alterations were identified from 272 genes in ER positive subtype while 448 non-synonymous variants were identified from 221 genes in ER negative subtype. PTEN is the most frequently altered gene in ER positive subtype (64%, 7/11) while ARID1A is the most frequently altered gene in ER negative subtype (50%, 4/8). We also identified alterations in ERRB3 (36%, 4/11), GNAS (36%, 4/11), and WHSC1 (27%, 3/11) in the ER positive subtype. WHSC1 R1126H and L1268P were shown to significantly increase cell viability, proliferation, migration, and survival. In addition, reduction in ER expression sensitized EEC-1 cell with WHSC1 L1268P mutant to Fulvestrant treatment. We revealed the mutational spectra of ER positive and ER negative EEC that could lead to better understanding of the biological mechanisms of endometrial cancer and may ultimately result in improvement of treatment options and patient prognosis.
Establishment of an immunofluorescence assay to detect IgM antibodies to Nipah virus using HeLa cells expressing recombinant nucleoprotein

Kaku Y, Park ES, Noguchi A, Inoue S, Lunt R, Malbas FF, et al.

J Virol Methods, 2019 07;269:83-87.
PMID: 30954461 DOI: 10.1016/j.jviromet.2019.03.009

A novel indirect fluorescent antibody test (IFAT) for detection of IgM against Nipah virus (NiV) was developed using HeLa 229 cells expressing recombinant NiV nucleocapsid protein (NiV-N). The NiV IFAT was evaluated using three panels of sera: a) experimentally produced sera from NiV-N-immunized/pre-immunized macaques, b) post-infection human sera associated with a Nipah disease outbreak in the Philippines in 2014, and c) human sera from a non-exposed Malaysian population. Immunized macaque sera showed a characteristic granular staining pattern of the NiV-N expressed antigen in HeLa 229 cells, which was readily distinguished from negative-binding results of the pre-immunized macaque sera. The IgM antibody titers in sequential serum samples (n = 7) obtained from three Nipah patients correlated well with previously published results using conventional IgM capture ELISA and SNT serology. The 90 human serum samples from unexposed persons were unreactive by IFAT. The IFAT utilizing NiV-N-expressing HeLa 229 cells to detect IgM antibody in an early stage of NiV infection is an effective approach, which could be utilized readily in local laboratories to complement other capabilities in NiV-affected countries.
Fulltext Discordance between Fasting Plasma Glucose (FPG) and HbA1c in Diagnosing Diabetes and Pre-diabetes in The Malaysian Cohort

Abdul Murad NA, Abdullah N, Kamaruddin MA, Abd Jalal N, Ismail N, Yusof NAM, et al.

J ASEAN Fed Endocr Soc, 2021;36(2):127-132.
PMID: 34966195 DOI: 10.15605/jafes.036.02.02

OBJECTIVE: In this present study, we aim to evaluate the accuracy of the HbA1c relative to fasting plasma glucose (FPG) in the diagnosis of diabetes and pre-diabetes among The Malaysian Cohort (TMC) participants.
METHODOLOGY: FPG and HbA1c were taken from 40,667 eligible TMC participants that have no previous history of diabetes, aged between 35-70 years and were recruited from 2006 - 2012. Participants were classified as normal, diabetes and pre-diabetes based on the 2006 World Health Organization (WHO) criteria. Statistical analyses were performed using ANOVA and Chi-square test, while Pearson correlation and Cohen's kappa were used to examine the concordance rate between FPG and HbA1c.
RESULTS: The study samples consisted of 16,224 men and 24,443 women. The prevalence of diabetes among the participants was 5.7% and 7.5% according to the FPG and HbA1c level, respectively. Based on FPG, 10.6% of the participants had pre-diabetes but this increased to 14.2% based on HbA1c (r=0.86; P<0.001). HbA1c had a sensitivity of 58.20 (95% CI: 56.43, 59.96) and a specificity of 98.59 (95% CI: 98.46, 98.70).
CONCLUSION: A higher prevalence of pre-diabetes and diabetes was observed when using HbA1c as a diagnosis tool, suggesting that it could possibly be more useful for early detection. However, given that HbA1c may also have lower sensitivity and higher false positive rate, several diagnostic criteria should be used to diagnose diabetes accurately.
Quantification of Her-2/Neu gene in breast cancer patients using real time-polymerase chain reaction (Q-PCR) and correlation with immunohistochemistry findings

Abdul Murad NA, Razak ZA, Hussain RM, Syed Hussain SN, Ko Ching Huat C, Che Md Ali SA, et al.

Asian Pac J Cancer Prev, 2013;14(3):1655-9.
PMID: 23679251

BACKGROUND: HER-2/neu is a proto-oncogene that encodes a transmembrane tyrosine kinase growth factor which is crucial for stimulating growth and cellular motility. Overexpression of HER-2/neu is observed in 10-35% of human breast cancers and is associated with pathogenesis, prognosis as well as response to therapy. Given the imperative role of HER-2/neu overexpression in breast cancer, it is important to determine the magnitude of amplification which may facilitate a better prognosis as well as personalized therapy in affected patients. In this study, we determined HER-2/neu protein expression by immunohistochemistry (IHC) concurrently with HER-2/neu DNA amplification by quantitative real time-polymerase chain reaction (Q-PCR).
MATERIALS AND METHODS: A total of 53 paired tissue samples from breast cancer patients were frozen-sectioned to characterize the tumour and normal tissues. Only tissues with 80% tumour cells were used in this study. For confirmation, Q-PCR was used to determine the HER-2/neu DNA amplification.
RESULTS: We found 20/53 (37.7%) of the tumour tissues to be positive for HER-2/neu protein overexpression using IHC. Out of these twenty, only 9/53 (17%) cases were in agreement with the Q-PCR results. The concordance rate between IHC and Q-PCR was 79.3%. Approximately 20.7% of positive IHC cases showed no HER-2/neu gene amplification using Q-PCR.
CONCLUSION: In conclusion, IHC can be used as an initial screening method for detection of the HER-2/neu protein overexpression. Techniques such as Q-PCR should be employed to verify the IHC results for uncertain cases as well as determination of HER-2/neu gene amplification.
Validation of immunogenic PASD1 peptides against HLA-A*24:02 colorectal cancer

Soh JE, Abu N, Sagap I, Mazlan L, Yahaya A, Mustangin M, et al.

Immunotherapy, 2019 10;11(14):1205-1219.
PMID: 31478431 DOI: 10.2217/imt-2019-0073

Colorectal cancer is the third commonest malignancy in Asia including Malaysia. The immunogenic cancer-testis antigens, which are expressed in a variety of cancers but with limited expression in normal tissues except the testis, represent an attractive approach to improve treatment options for colorectal cancer. We aimed to validate four PASD1 peptides as the immunotherapeutic targets in colorectal cancer. First, PASD1 mRNA and protein expression were determined via real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. The PASD1 peptides specific to HLA-A*24:02 were investigated using IFN-y-ELISpot assay, followed by the cytolytic and granzyme-B-ELISpot assays to analyze the cytolytic effects of CD8+ T cells. Gene and protein expressions of PASD1 were detected in 20% and 17.3% of colorectal cancer samples, respectively. PASD1(4) peptide was shown to be immunogenic in colorectal cancer samples. CD8+ T cells raised against PASD1(4) peptide were able to lyze HLA-A*24:02+ PASD1+ cells. Our results reveal that PASD1(4) peptide represents a potential target for colorectal cancer.
Dengue epidemic in Malaysia: urban versus rural comparison of dengue immunoglobulin G seroprevalence among Malaysian adults aged 35-74 years

Azami NAM, Moi ML, Salleh SA, Neoh HM, Kamaruddin MA, Jalal NA, et al.

Trans R Soc Trop Med Hyg, 2020 11 06;114(11):798-811.
PMID: 32735681 DOI: 10.1093/trstmh/traa056

BACKGROUND: A periodic serosurvey of dengue seroprevalence is vital to determine the prevalence of dengue in countries where this disease is endemic. This study aimed to determine the prevalence of dengue immunoglobulin G (IgG) seropositivity among healthy Malaysian adults living in urban and rural areas.
METHODS: A total of 2598 serum samples (1417 urban samples, 1181 rural samples) were randomly collected from adults ages 35-74 y. The presence of the dengue IgG antibody and neutralising antibodies to dengue virus (DENV) 1-4 was determined using enzyme-linked immunosorbent assay and the plaque reduction neutralisation test assay, respectively.
RESULTS: The prevalence of dengue IgG seropositivity was 85.39% in urban areas and 83.48% in rural areas. The seropositivity increased with every 10-y increase in age. Ethnicity was associated with dengue seropositivity in urban areas but not in rural areas. The factors associated with dengue seropositivity were sex and working outdoors. In dengue IgG-positive serum samples, 98.39% of the samples had neutralising antibodies against DENV3, but only 70.97% of them had neutralising antibodies against DENV4.
CONCLUSION: The high seroprevalence of dengue found in urban and rural areas suggests that both urban and rural communities are vital for establishing and sustaining DENV transmission in Malaysia.
Fulltext Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress

Soon BH, Abdul Murad NA, Then SM, Abu Bakar A, Fadzil F, Thanabalan J, et al.

Front Physiol, 2017;8:231.
PMID: 28484394 DOI: 10.3389/fphys.2017.00231

The role of mitochondria in tumorigenesis has regained much attention as it could dysregulate cellular energetics, oxidative stress and apoptosis. However, the role of mitochondria in different grade gliomasis still unknown. This study aimed to identify mitochondrial DNA (mtDNA) sequence variations that could possibly affect the mitochondrial functions and also the oxidative stress status. Three different grades of human glioma cell lines and a normal human astrocyte cell line were cultured in-vitro and tested for oxidative stress biomarkers. Relative oxidative stress level, mitochondria activity, and mitochondrial mass were determined by live cell imaging with confocal laser scanning microscope using CM-H2DCFDA, MitoTracker Green, and MitoTracker Orange stains. The entire mitochondrial genome was sequenced using the AffymetrixGeneChip Human Mitochondrial Resequencing Array 2.0. The mitochondrial sequence variations were subjected to phylogenetic haplogroup assessment and pathogenicity of the mutations were predicted using pMUT and PolyPhen2. The Grade II astrocytoma cells showed increased oxidative stress wherea high level of 8-OHdG and oxidative stress indicator were observed. Simultaneously, Grade II and III glioma cells showed relatively poor mitochondria functions and increased number of mutations in the coding region of the mtDNA which could be due to high levels of oxidative stress in these cells. These non-synonymous mtDNA sequence variations were predicted to be pathogenic and could possibly lead to protein dysfunction, leading to oxidative phosphorylation (OXPHOS) impairment, mitochondria dysfunction and could create a vicious cycle of oxidative stress. The Grade IV cells had no missense mutation but preserved intact mitochondria and excellent antioxidant defense mechanisms thus ensuring better survival. In conclusion, Grade II and III glioma cells demonstrated coding region mtDNA mutations, leading to mitochondrial dysfunction and higher oxidative stress.
Fulltext 10-Year Cardiovascular Disease Risk Estimation Based on Lipid Profile-Based and BMI-Based Framingham Risk Scores across Multiple Sociodemographic Characteristics: The Malaysian Cohort Project

Borhanuddin B, Mohd Nawi A, Shah SA, Abdullah N, Syed Zakaria SZ, Kamaruddin MA, et al.

ScientificWorldJournal, 2018;2018:2979206.
PMID: 30111990 DOI: 10.1155/2018/2979206

Cardiovascular disease (CVD) leads to high morbidity and mortality rate worldwide. Therefore, it is important to determine the risk of CVD across the sociodemographic factors to strategize preventive measures. The current study consisted of 53,122 adults between the ages of 35 and 65 years from The Malaysian Cohort project during recruitment phase from year 2006 to year 2012. Sociodemographic profile and physical activity level were assessed via self-reported questionnaire, whereas relevant CVD-related biomarkers and biophysical variables were measured to determine the Framingham Risk Score (FRS). The main outcome was the 10-year risk of CVD via FRS calculated based on lipid profile and body mass index (BMI) associated formulae. The BMI-based formula yielded a higher estimation of 10-year CVD risk than the lipid profile-based formula in the study for both males (median = 13.2% and 12.7%, respectively) and females (median = 4.3% and 4.2%, respectively). The subgroup with the highest risk for 10-year CVD events (based on both FRS formulae) was the Malay males who have lower education level and low physical activity level. Future strategies for the reduction of CVD risk should focus on screening via BMI-based FRS in this at-risk subpopulation to increase the cost-effectiveness of the prevention initiatives.
Study name: The Malaysian Cohort (TMC) project

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