Adzrool Idzwan Ismail

Detection of CYP2C19 Genetic Variants in Malaysian Orang Asli from Massively Parallel Sequencing Data.

The human cytochrome P450 (CYP) is a superfamily of enzymes that have been a focus in research for decades due to their prominent role in drug metabolism. CYP2C is one of the major subfamilies which metabolize more than 10% of all clinically used drugs. In the context of CYP2C19, several key genetic variations that alter the enzyme’s activity have been identified and catalogued in the CYP allele nomenclature database. In this study, we investigated the presence of well-established variants as well as novel polymorphisms in the CYP2C19 gene of 62 Orang Asli from the Peninsular Malaysia. A total of 449 genetic variants were detected including 70 novel polymorphisms; 417 SNPs were located in introns, 23 in upstream, 7 in exons, and 2 in downstream regions. Five alleles and seven genotypes were inferred based on the polymorphisms that were found. Null alleles that were observed include CYP2C19*3 (6.5%), *2 (5.7%) and *35 (2.4%) whereas allele with increased function *17 was detected at a frequency of 4.8%. The normal metabolizer genotype was the most predominant (66.1%), followed by intermediate metabolizer (19.4%), rapid metabolizer (9.7%) and poor metabolizer (4.8%) genotypes. Findings from this study provide further insights into the CYP2C19 genetic profile of the Orang Asli as previously unreported variant alleles were detected through the use of massively parallel sequencing technology platform. The systematic and comprehensive analysis of CYP2C19 will allow uncharacterized variants that are present in the Orang Asli to be included in the genotyping panel in the future.

Systematic characterization and comparison of the CYP2C9 variability of the Orang Asli in Malaysia with 12 populations.

We conducted a systematic characterization of CYP2C9 variants in 61 Orang Asli and 96 Singaporean Malays using the whole genome sequences data and compared the variants with the other 11 HapMap populations. The frequency of rs1057910 (CYP2C9*3) is the highest in the Orang Asli compared to other populations. Three alleles with clinical implication were detected in the Orang Asli while 2 were found in the Singaporean Malays. Large numbers of the Orang Asli are predicted to have reduced metabolic capacity and therefore they would require a lower dose of drugs which are metabolized by CYP2C9. They are also at increased risks of adverse effects and therapeutic failures. A large number of CYP2C9 variants in the Orang Asli were not in the Hardy Weinberg Equilibrium which could be due to small sample size or mutations that disrupt the equilibrium of allele frequencies. In conclusion, different polymorphism patterns, allele frequencies, genotype frequencies and LD blocks are observed between the Orang Asli, the Singaporean Malays and the other populations. The study provided new information on the genetic polymorphism of CYP2C9 which is important for the implementation of precision medicine for the Orang Asli.

A study on the genetic polymorphisms of CYP3A5 among the Orang Asli in Malaysia using a next generation sequencing platform

Abstract Background: CYP3A5 is the predominant sub-family of biotransformation enzymes in the liver and the genetic variations in CYP3A5 are an important determinant of inter-individual and inter-ethnic differences in CYP3A-mediated drug disposition and response. Aim: This study aims to investigate the genetic polymorphisms of CYP3A5 among the Orang Asli in Peninsular Malaysia using a next generation sequencing platform. Methods: Genomic DNAs were extracted from blood samples of the three main Orang Asli tribes and whole-genome sequencing was performed. Results: A total of 61 single nucleotide polymorphisms were identified and all the SNPs were located in introns except rs15524, which is in the 3’UTR, and 11 of these polymorphisms were novel. Two allelic variants and three genotypes were identified in the Orang Asli. The major allelic variant was the non-functional CYP3A5*3 (66.4%). The percentages of Orang Asli with CYP3A5*3/*3 (47.2%) and CYP3A5*1/*3 (38.1%) genotypes are more than twice the percentage of Orang Asli with CYP3A5*1/*1 (14.8%) genotype. Almost half of the Orang Asli harboured CYP3A5 non-expressor genotype (CYP3A5*3/*3). Conclusions: The predominance of the CYP3A5 non-expressor genotype among the Orang Asli was unravelled and the findings in this study may serve as a guide for the optimisation of pharmacotherapy for the Orang Asli community.

The analysis of job related stress and health related quality of life (HRQoL) of lecturers: Using SPSS 16 and Structural Equation Modeling

In Malaysia, academicians have been one of the most important groups in the society that is at a higher risk of suffering from job related stress. A cross sectional study was conducted in the middle of the academic semester of a university from 25th September 2011 to 10th November 2011 to investigate factors that affect job related stress and to find out if job related stress in turn influence the health related quality of life (HRQoL) of lecturers. It was also conducted to find out if HRQoL of lecturers differ between gender and age group. Comparison of HRQoL was also made between the lecturers and the general Malaysian population norm. The target population for this study was lecturers at one of the public universities in Malaysia with a size of 4500 lecturers. Data was obtained via survey using SF36v2 (questions on HRQoL) and the Occupation Stress Indicator (OSI) to measure job related stress and was analyzed using SPSS16 and Structural Equation Modeling (SEM) Sample size calculated was 393 using IBM Complex sampling for cluster, stratified and simple random techniques. However, only 277 lecturers responded with a response rate of 57.7%. Nevertheless, analysis using Structural Equation Modeling (SEM) could still be conducted since a minimum of 200 respondents is suggested. The results showed that all the mean scores for the eight domains of SF36v2 are lower than that of the general Malaysian population norm. There are also significant differences in the mean scores for HRQoL domains between gender and age group. It is also discovered that there is significant and direct impact of conflict, work burden and time pressure on job stress which in turn influence health related quality of life. In conclusion, the management of this public university should pay attention to the results of this study by looking into ways of reducing job stress to enhance the HRQoL of lecturers. With better quality of life, it is hoped that this will improve their job performance and productivity.

Box-Jenkins Method of analysing rate of cancer deaths at a public university hospital in east coast of Malaysia

Cancer is one of the principal causes of death in Malaysia. This study was performed to determine the pattern of rate of cancer mortality at a public hospital in Malaysia over an 11 year period from year 2001 to 2011; the best fitted model using Box-Jenkins Method of analysis to forecast the rate of cancer mortality and to forecast the rate for the next two years (2012 to 2013). The Secondary data for this study was obtained from a public university hospital located at the East Coast of Malaysia. The data were medical records of patients who died due to cancer from the year 2001 until 2011, with 663 cases. The cancer cases were classified according to ICD10 (10th Revision International Classification of Diseases). The medical records include socio-demographic background of patients such as registration, age, gender, race, ward and diagnosis. SPPS Version 19 and Minitab 16.0 were used to analyse the data. Malay patients (88.10%) and males (51.30%) were the highest percentages for the overall 11 years death rate of cancer at this hospital. Lung and breast cancer were the most cancer deaths among both gender. The highest death rate (29.60%) is also among patients aged 61 and above. The best model used for forecasting the rate of cancer deaths is ARMA (1, 3). The forecasting values for the rate of cancer deaths for January 2012 to April 2012 range from 5.91% to 6.13%. However, the forecast saw a stable overall cancer mortality trend of 6.14% for May 2012 to November 2013.

Notice of Retraction Neuropolitics and political non-apology: A proposed variable framework

Malaysias constitution requires a general election to be held at least once every five years, the next one being the 13th General Election (PRU13) scheduled for 2013. However, the prime minister can also request for Parliament to be dissolved at any time within that five years. Politicians, especially from the ruling coalition, are scrambling to ensure another victory in PRU13. Similarly, the opposition will try their best to win through the democratic process of voting. Hence, the current political scenarios have continued to see remarks, insinuations and even outright accusations on certain issues among the politicians so as to gain public attention. Some will even go to the extent of digging dubious pasts of the individuals and engaging in character smearing resulting in court cases to prove their innocence while others will demand for public apology. However, not all politicians will apologize and non-apology will drag the case for an indefinite time. The unwillingness to apologize requires much thought and deliberation in the amygdala. Consequently, through purposive sampling and the analyses of preliminary interviews with politicians and political analysts, this paper will propose and provide insights into the construct of a variable framework that will form the foundation of neuropolitically-based non-apologetic behavior among politicians in Malaysia. Understanding the politicians unwillingness to publicly apologize will demystify the situation and the rakyat will be well-informed of the behavioral and psychological reasons behind the non-apology.

RETRACTED ARTICLE: Neuropolitics and political non-apology: A proposed variable framework

Malaysias constitution requires a general election to be held at least once every five years, the next one being the 13th General Election (PRU13) scheduled for 2013. However, the prime minister can also request for Parliament to be dissolved at any time within that five years. Politicians, especially from the ruling coalition, are scrambling to ensure another victory in PRU13. Similarly, the opposition will try their best to win through the democratic process of voting. Hence, the current political scenarios have continued to see remarks, insinuations and even outright accusations on certain issues among the politicians so as to gain public attention. Some will even go to the extent of digging dubious pasts of the individuals and engaging in character smearing resulting in court cases to prove their innocence while others will demand for public apology. However, not all politicians will apologize and non-apology will drag the case for an indefinite time. The unwillingness to apologize requires much thought and deliberation in the amygdala. Consequently, through purposive sampling and the analyses of preliminary interviews with politicians and political analysts, this paper will propose and provide insights into the construct of a variable framework that will form the foundation of neuropolitically-based non-apologetic behavior among politicians in Malaysia. Understanding the politicians unwillingness to publicly apologize will demystify the situation and the rakyat will be well-informed of the behavioral and psychological reasons behind the non-apology.

An interpretation of photography as an art and communication

Photography is a visual representation, which highlights an act of seeing to establish subject matter in the surroundings. These would be described, explained and visualized with the content of the emotional experience. The process of communication starts when the information sources encode or produce a set of messages in the mode of speech, written form, picture or other media to other parties. In a communication process, photograph is used as medium of persuasion as it controls the emotions of the reviewer. The production of an image in communicating with its viewers undergoes a critical process. Thus this paper explores how society perceives and holds attitudes in interpreting and describing a photograph as a form of arts and media in a communication process.