Relationship of selective complement markers with schizophrenia.

Immune system dysregulation may be involved in schizophrenia, but biomarker studies have thus far reported inconsistent findings. The relationship of plasma levels of complement markers C3 and C4, with schizophrenia, sociodemographic and clinico-psychological factors were here studied in 183 patients and 212 controls. C3 and C4 levels were significantly higher in the patients and in subjects with elevated C-reactive protein (CRP), and positively correlated with body mass index (BMI) (p < 0.05). Schizophrenia, BMI, and CRP were significant predictors for C3 and C4 levels in multivariate analyses (p < 0.001). In conclusion, complements C3 and C4 are potential peripheral biomarkers in schizophrenia.

Leucocytic DNA Methylation of Interleukin-6 Promoter Reduction in Pre-Hypertensive Young Adults

@#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

DNA methylation of membrane-bound catechol-O-methyltransferase in Malaysian schizophrenia patients.

AIM: This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relations with the clinical variables of schizophrenia patients. METHODS: We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays. The extracted DNA was bisulfite converted, and the percentage methylation ratio value was calculated based on the results following a MethyLight protocol analysis. RESULTS: The percentage methylation ratio of COMT was lower in schizophrenia than it was in the healthy controls (P < 0.001) and was different between the body mass index (P = 0.003) and antipsychotic (P = 0.004) groups. The COMT DNA methylation rate was lower in patients receiving atypical antipsychotics (P = 0.004) and risperidone (P = 0.049) as compared to typical antipsychotics. The Excitement and Depressed subdomains of the Positive and Negative Syndrome Scale were inversely related (P < 0.001) and therefore predictors (Excitement: b = -11.396, t = -4.760, P < 0.001; Depressed: b = -7.789, t = -3.487, P = 0.001) of COMT DNA methylation. CONCLUSION: Our results suggested that the methylation level was affected by the severity of the clinical symptoms of schizophrenia and might also be influenced by pharmacological treatment. The epigenetic alteration of COMT in the peripheral blood could be a potential peripheral biomarker of schizophrenia.

Reelin (RELN) DNA methylation in the peripheral blood of schizophrenia.

The epigenetic changes of RELN that are involved in the development of dopaminergic neurons may fit the developmental theory of schizophrenia. However, evidence regarding the association of RELN DNA methylation with schizophrenia is far from sufficient, as studies have only been conducted on a few limited brain samples. As DNA methylation in the peripheral blood may mirror the changes taking place in the brain, the use of peripheral blood for a DNA methylation study in schizophrenia is feasible due to the scarcity of brain samples. Therefore, the aim of our study was to examine the relationship of DNA methylation levels of RELN promoters with schizophrenia using genomic DNA derived from the peripheral blood of patients with the disorder. The case control studies consisted of 110 schizophrenia participants and 122 healthy controls who had been recruited from the same district. After bisufhite conversion, the methylation levels of the DNA samples were calculated based on their differences of the Cq values assayed using the highly sensitive real-time MethyLight TaqMan® procedure. A significantly higher level of methylation of the RELN promoter was found in patients with schizophrenia compared to controls (p = 0.005) and also in males compared with females (p = 0.004). Subsequently, the RELN expression of the methylated group was 25 fold less than that of the non-methylated group. Based upon the assumption of parallel methylation changes in the brain and peripheral blood, we concluded that RELN DNA methylation might contribute to the pathogenesis of schizophrenia. However, the definite effects of methylation on RELN function during development and also in adult life still require further elaboration.

Anti-atherosclerotic Effects of Eurycoma Longifolia (Tongkat Ali) in Rats Fed on High-fat Diet

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.

MGMT and SPOCK2 Promoter Methylation in Diffuse Large B-Cell Lymphoma: A Study in Two Tertiary Health Centres in the East Coast of Malaysia / Jurnal Sains Kesihatan Malaysia

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.

Disrupted-in-Schizophrenia-1 SNPs and Susceptibility to Schizophrenia: Evidence from Malaysia.

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.

Relationship of psychological symptoms, antipsychotics and social data with psychosocial function in schizophrenia patients in Malaysia.

INTRODUCTION: The present study investigated the relationship between psychological symptoms and psychosocial function and the role of relevant sociodemographic data and antipsychotic use in the prediction of psychosocial function among multiracial schizophrenia outpatients in Malaysia. METHODS: A total of 223 participants were recruited in this cross-sectional study conducted from December 2010 to April 2011. Psychological symptoms were assessed using the Positive and Negative Syndrome Scale whilst the psychosocial function was assessed using the Personal and Social Performance scale. Sociodemographic and treatment variables were gathered through interview or review of the medical records. RESULTS: All dimensions of psychosocial functions were inversely correlated with Positive and Negative Syndrome Scale sub-domains. Only the disorganization sub-domain significantly predicts all dimensions of psychosocial function. For social data, body mass index and employment status were significant predictors of all dimensions of psychosocial functions. Typical antipsychotics significantly predict social function negatively as compared to sulpiride (ß = -0.152, P = 0.028). DISCUSSION: We found that the relationship between psychological symptoms and psychosocial functions were relatively consistent with the findings from the Caucasian population. Additionally, disorganization was the only significant predictor of all dimensions of psychosocial functions. This further emphasized the importance of cognition in psychosocial function. The roles of sulpiride, body mass index and employment status as predictors of psychosocial function were also discussed.