1.MGMT and SPOCK2 Promoter Methylation in Diffuse Large B-Cell Lymphoma: A Study in Two Tertiary Health Centres in the East Coast of Malaysia
Norafiza Zainuddin ; Lailatul Jalilah Mohd Ridah ; Aqilah Nabihah Omar ; Norlelawati A. Talib ; Naznin Muhammad ; Faezahtul Arbaeyah Hussain
Malaysian Journal of Health Sciences 2017;15(2):77-82
MGMT (O6
-Methylguanine-DNA Methyltransferase) suppresses tumor development by removing alkyl adduct, while
SPOCK2 (SPARC/Osteonectin CWCV and Kazal-like domains proteoglycan) abolishes the inhibition of membrane-type
matrix metalloproteinases (MT-MMP) which leads to angiogenesis. Hence, MGMT methylation may initiate malignant cells
transformation. In contrast, SPOCK2 methylation is hypothesized not to be a common event in diffuse large B-cell lymphoma
(DLBCL). In this study, we examined the methylation status of MGMT and SPOCK2 in DLBCL as in Malaysia the information
is extremely lacking. A total of 88 formalin-fixed paraffin-embedded tissue of patients diagnosed with DLBCL from the
year 2006 to 2013 were retrieved from Hospital Universiti Sains Malaysia, Kelantan and Hospital Tengku Ampuan Afzan,
Pahang. Methylation-specific polymerase chain reaction (MSP) was used to examine the methylation status of both genes.
Interestingly, methylation of MGMT was detected in all the 88 DLBCL samples, whereas SPOCK2 was found to be methylated
in 83 of 88 (94.3%) DLBCL cases. Our study showed a remarkably high percentage of promoter methylation of both
MGMT and SPOCK2 genes. Our finding also negates initial expectation that SPOCK2 methylation would be an uncommon
event in the majority of DLBCL cases. This study has shown a very high percentage of promoter methylation of MGMT and
SPOCK2 in the DLBCL cases studied by MSP, using archival lymphoma tissues. Nonetheless, additional research is needed
to quantitatively evaluate MGMT and SPOCK2 methylation, and to analyse gene expression and/or protein expression in
order to further understand the role of MGMT and SPOCK2 methylation in the pathogenesis of DLBCL.
2.Anti-atherosclerotic Effects of Eurycoma Longifolia (Tongkat Ali) in Rats Fed on High-fat Diet
Fakhria Al-Joufi ; Anil K. Saxena ; Imad M. Al-Ani ; Norlelawati A. Talib ; Norsidah Ku -Zaifah
The International Medical Journal Malaysia 2017;16(1):83-90
Atherosclerosis in cardiovascular disease (CVD) is a growing health problem, especially in developing
countries. Hyperlipidemia is known as a dominant risk factor for the development of atherosclerosis. This
study was designed to investigate the effects of Eurycoma Longifolia (EL) also known as Malaysian Ginseng/
Tongkat Ali on the testosterone level, biochemical changes of lipid profile and intima media thickness (IMT)
in rats fed on high-fat diet. Twenty young, adult male Sprague-Dawley (SD) rats were housed for 12 weeks.
After one week of acclimatization, they were randomly divided into four groups of 5 animals each and
treated for 12 weeks as follow: Group ND was given only normal diet, group NDEL was given normal diet and
EL extracts (15mg/kg) dissolved in distilled water, group HFD was given only high fat diet and group HFDEL
was given high fat diet and EL extracts (15mg/kg). Rats which were treated with EL (NDEL and HFDEL)
showed a significant increase (p<0.05) in the testosterone levels. There was a significant decrease (p<0.05)
in triglyceride (TG) in HFDEL group compered to HFD group. The histological sections of aortas revealed a
significant decrease (p<0.05) in IMT in HFDEL as compared with HFD group. No histological changes were
observed in NDEL group compared with ND group and there was no significant difference in IMT values
between NDEL and ND. These findings suggest that EL is a promising protective agent against atherosclerosis
induced by high-fat diet.
3.Disrupted-in-Schizophrenia-1 SNPs and Susceptibility to Schizophrenia: Evidence from Malaysia.
A Talib NORLELAWATI ; Abdullah KARTINI ; Kuzaifah NORSIDAH ; Musa RAMLI ; Abdul Razak TARIQ ; Wan Taib WAN ROHANI
Psychiatry Investigation 2015;12(1):103-111
OBJECTIVE: Even though the role of the DICS1 gene as a risk factor for schizophrenia is still unclear, there is substantial evidence from functional and cell biology studies that supports the connection of the gene with schizophrenia. The studies associating the DISC1 gene with schizophrenia in Asian populations are limited to East-Asian populations. Our study examined several DISC1 markers of schizophrenia that were identified in the Caucasian and East-Asian populations in Malaysia and assessed the role of rs2509382, which is located at 11q14.3, the mutual translocation region of the famous DISC1 translocation [t (1; 11) (p42.1; q14.3)]. METHODS: We genotyped eleven single-neucleotide polymorphism (SNPs) within or related to DISC1 (rs821597, rs821616, rs4658971, rs1538979, rs843979, rs2812385, rs1407599, rs4658890, and rs2509382) using the PCR-RFLP methods. RESULTS: In all, there were 575 participants (225 schizophrenic patients and 350 healthy controls) of either Malay or Chinese ethnicity. The case-control analyses found two SNPs that were associated with schizophrenia [rs4658971 (p=0.030; OR=1.43 (1.35-1.99) and rs1538979-(p=0.036; OR=1.35 (1.02-1.80)] and rs2509382-susceptibility among the males schizophrenics [p=0.0082; OR=2.16 (1.22-3.81)]. This is similar to the meta-analysis findings for the Caucasian populations. CONCLUSION: The study supports the notion that the DISC1 gene is a marker of schizophrenia susceptibility and that rs2509382 in the mutual DISC1 translocation region is a susceptibility marker for schizophrenia among males in Malaysia. However, the finding of the study is limited due to possible genetic stratification and the small sample size.
Asian Continental Ancestry Group
;
Case-Control Studies
;
Humans
;
Malaysia*
;
Male
;
Polymorphism, Single Nucleotide*
;
Risk Factors
;
Sample Size
;
Schizophrenia*
4.Leucocytic DNA Methylation of Interleukin-6 Promoter Reduction in Pre-Hypertensive Young Adults
Wan Fatein Nabeila Wan Omar ; Aszrin Abdullah ; Norlelawati A Talib ; Azarisman Shah Mohd Shah ; Jamalludin AJamalludin Ab RahmanAb Rahman
Malaysian Journal of Medical Sciences 2019;26(6):46-54
Background: Pre-hypertension is associated with increased risk of cardiovascular disease.
Chronic inflammation plays an important role in the pathophysiology of essential hypertension,
with epigenetic dysregulation involvement. Nevertheless, the role of DNA methylation in prehypertensive
state is unknown. The aim of this study was to investigate the association between
DNA methylation level of interleukin-6 (IL-6) promoter in pre-hypertensive (PreHT) and
normotensive (NT) young adults.
Methods: A total of 80 NT and 80 PreHT healthy subjects aged between 18–45 years were
recruited in Kuantan, Pahang, Malaysia using an observational cross-sectional study approach.
DNA methylation level of IL-6 promoter in peripheral leukocytes were measured using bisulphite
conversion and MethyLight assay.
Results: There was no significant difference in age between NT and PreHT (P = 0.655).
The mean blood pressure was 110(8)/73(5) mmHg in NT and 125(7)/82(5) mmHg in PreHT
subjects. The IL-6 promoter methylation level was significantly lower in PreHT compared to NT
subjects (P < 0.001).
Conclusion: The current study demonstrates that hypomethylation of IL-6 promoter
was associated with pre-hypertension in young adults. Thus, IL-6 methylation could be used as
an early indicator for predicting hypertension and related risk of cardiovascular diseases in prehypertensive
subjects. Gene expression and longitudinal studies are warranted to examine the
methylation effect on IL-6 expression over time