Diversity and Differentiation

New ways of working are being embraced by early childhood educators as they cope with demands from national reforms and changing communities. While reformers are pressing for social equity and improved outcomes for families and children, communities are diverging in terms of ethnicity, culture, language and socioeconomic status. As a consequence, early childhood educators are being challenged to expand their existing repertoire of practices in order to more effectively provide quality learning experiences for every child in their care. Practice enhancement and differentiated pedagogy are needed to address the additional needs of an increasing number of diverse learners. Community expectations are particularly focused on better educational supports for children in five cluster areas: • Culturally diverse and Indigenous backgrounds • ‘at risk’ because of socio-economic and abuse conditions • Communicative, emotional and behavioural disorders • Disabilities and learning difficulties and • Recognised gifts and talents This chapter focuses on some everyday ractices that can be used strategically to better support all children, including those with additional educational needs. All practices are well supported in the literature and are substantiated by either research findings or strong, socially determined values. They also very ‘doable’ and sustainable in today’s dynamic and multifaceted early childhood settings. Seven keys practices will be introduced, together with examples of how they can be applied to both enhance the learning of individual children and to strengthen a sense of group belonging. The practices are: • Having positive beliefs about all children • Learning about each child • Building meaningful relationships around the child • Creating supportive learning environments for the child • Providing engaging learning experiences for the child • Differentiating instruction for the child • Using child progress data to improve learning and teaching

Analysing the Sri Lankan conflict using Michael Mann's four-dimensional model of social power

This thesis provides an overview of the Sri Lankan civil war with a view to identifying some of the factors that contributed to the dispute between the Sri Lankan government and the Liberation Tigers of Tamil Eelam. It adopts a multi-causal explanation of the conflict by reference to the theories of social power developed by Michael Mann. The conflict has been variously described as an ethnic or political conflict, or has been characterised as a determined by a number of interacting factors (including colonialism, ethnicity, religion, economy, politics and globalisation). Mann’s four-dimensional model of social power is deployed to analyse the causal relationships, together with their inter-connections, which clarify the origins of the dispute. It argues that Mann’s theoretical framework helps to highlight some of the interconnected elements that contributed to the conflict.

Students' perceptions of teacher biases : experimental economics in schools

We put forward a new experimental economics design with monetary incentives to estimate students’ perceptions of grading discrimination. We use this design in a large field experiment which involved 1,200 British students in grade 8 classrooms across 29 schools. In this design, students are given an endowment they can invest on a task where payoff depends on performance. The task is a written verbal test which is graded non anonymously by their teacher, in a random half of the classrooms, and graded anonymously by an external examiner in the other random half of the classrooms. We find significant evidence that students’ choices reflect perceptions of biases in teachers’ grading practices. Our results show systematic gender interaction effects: male students invest less with female teachers than with male teachers while female students invest more with male teachers than with female teachers. Interestingly, female students’ perceptions are not in line with actual discrimination: Teachers tend to give better grades to students of their own gender. Results do not suggest that ethnicity and socioeconomic status play a role. .

ICT shared services in the higher education sector : foundations, benefits, success factors and issues

Universities are more and more challenged by the emerging global higher education market, facilitated by advances in Information and Communication Technologies (ICT). This requires them to reconsider their mission and direction in order to function effectively and efficiently, and to be responsive to changes in their environment. In the face of increasing demands and competitive pressures, Universities like other companies, seek to continuously innovate and improve their performance. Universities are considering co-operating or sharing, both internally and externally, in a wide range of areas to achieve cost effectiveness and improvements in performance. Shared services are an effective model for re-organizing to reduce costs, increase quality and create new capabilities. Shared services are not limited to the Higher Education (HE) sector. Organizations across different sectors are adopting shared services, in particular for support functions such as Finance, Accounting, Human Resources and Information Technology. While shared services has been around for more than three decades, commencing in the 1970’s in the banking sector and then been adopted by other sectors, it is an under researched domain, with little consensus on the most fundamental issues even as basic as defining what shared services is. Moreover, the interest in shared services within Higher Education is a global phenomenon. This study on shared services is situated within the Higher Education Sector of Malaysia, and originated as an outcome resulting from a national project (2005 – 2007) conducted by the Ministry of Higher Education (MOHE) entitled "Knowledge, Information Communication Technology Strategic Plan (KICTSP) for Malaysian Public Higher Education"- where progress towards more collaborations via shared services was a key recommendation. The study’s primary objective was to understand the nature and potential for ICT shared services, in particular in the Malaysian HE sector; by laying a foundation in terms of definition, typologies and research agenda and deriving theoretically based conceptualisations of the potential benefits of shared services, success factors and issues of pursuing shared services. The study embarked on this objective with a literature review and pilot case study as a means to further define the context of the study, given the current under-researched status of ICT shared services and of shared services in Higher Education. This context definition phase illustrated a range of unaddressed issues; including a lack of common understanding of what shared services are, how they are formed, what objectives they full fill, who is involved etc. The study thus embarked on a further investigation of a more foundational nature with an exploratory phase that aimed to address these gaps, where a detailed archival analysis of shared services literature within the IS context was conducted to better understand shared services from an IS perspective. The IS literature on shared services was analysed in depth to report on the current status of shared services research in the IS domain; in particular definitions, objectives, stakeholders, the notion of sharing, theories used, and research methods applied were analysed, which provided a firmer base to this study’s design. The study also conducted a detailed content analysis of 36 cases (globally) of shared services implementations in the HE sector to better understand how shared services are structured within the HE sector and what is been shared. The results of the context definition phase and exploratory phase formed a firm basis in the multiple case studies phase which was designed to address the primary goals of this study (as presented above). Three case sites within the Malaysian HE sector was included in this analysis, resulting in empirically supported theoretical conceptualizations of shared services success factors, issues and benefits. A range of contributions are made through this study. First, the detailed archival analysis of shared services in Information Systems (IS) demonstrated the dearth of research on shared services within Information Systems. While the existing literature was synthesised to contribute towards an improved understanding of shared services in the IS domain, the areas that are yet under-developed and requires further exploration is identified and presented as a proposed research agenda for the field. This study also provides theoretical considerations and methodological guidelines to support the research agenda; to conduct better empirical research in this domain. A number of literatures based a priori frameworks (i.e. on the forms of sharing and shared services stakeholders etc) are derived in this phase, contributing to practice and research with early conceptualisations of critical aspects of shared services. Furthermore, the comprehensive archival analysis design presented and executed here is an exemplary approach of a systematic, pre-defined and tool-supported method to extract, analyse and report literature, and is documented as guidelines that can be applied for other similar literature analysis, with particular attention to supporting novice researchers. Second, the content analysis of 36 shared services initiatives in the Higher Education sector presented eight different types of structural arrangements for shared services, as observed in practice, and the salient dimensions along which those types can be usefully differentiated. Each of the eight structural arrangement types are defined and demonstrated through case examples, with further descriptive details and insights to what is shared and how the sharing occurs. This typology, grounded on secondary empirical evidence, can serve as a useful analytical tool for researchers investigating the shared services phenomenon further, and for practitioners considering the introduction or further development of shared services. Finally, the multiple case studies conducted in the Malaysian Higher Education sector, provided further empirical basis to instantiate the conceptual frameworks and typology derived from the prior phases and develops an empirically supported: (i) framework of issues and challenges, (ii) a preliminary theory of shared services success, and (iii) a benefits framework, for shared services in the Higher Education sector.

The effectiveness of public sector asset management in Malaysia

Property is an important factor in all businesses production in order to function. Nourse (1990) quoted ¡°some businesses are real estate, all businesses use real estate¡±. In recent years, the management of property assets has become the focus of many organisations, including the non-real estate businesses. Good asset management is concerned with the effective utilisation of a property owner.s assets. It is the management process of ensuring that the portfolio of properties held meets the overall requirements of the users. In short, it is the process of identifying the user.s requirement and the rationalisation of property holdings to match that requirement best, followed by a monitoring and ongoing review of practice. In Malaysia, federal agencies and local authorities are among the largest property asset owners. Recently the federal government has released a Total Asset Management Manual (TAMM). It is at the preliminary stage of implementation. This thesis will study the international practices of asset management of public sector assets and assess the effectiveness of TAMM. This research will focus on current international practices for the effective management of public sector property assets. The current application in Malaysia will be highlighted, to determine the awareness and understanding of the current practices to the recently released TAMM. This research is an exploratory research. The basis of this research relies on the combination of qualitative and quantitative approach, whereby the qualitative approach focuses on the international practices and its application to the management of public sector property assets. Questionnaires survey will be conducted among the Malaysian public property assets managers and users in the quantitative approach to gauge the collective opinion on the current practices of TAMM and its implementation

Standardisation of plant and machinery valuation practices in Malaysia

Plant and machinery valuation is important to every company.s annual financial reporting. It is reported under the non-current assets section, and the valuers are generally employed to provide the up to date valuation of the non-current assets valuation such as property, plant and equipment that can make up to 80% of the total assets of a company. The valuation of plant and machinery is also important for other purposes such as securing loan facilities, sales, takeover, insurance and auction. The application of 2005 International Financial Reporting Standard (IFRS) has a subsequent impact on the financial sector, as a whole. The accountants have to choose between the Historical Cost approach and Market Value approach in determining the value of the client.s assets. In Malaysia, the implementation of IFRS has a domino effect on the financial system, especially for plant and machinery valuation for financial reporting. The comparison data for plant and machinery valuation is limited unlike land and building valuation. The question of Malaysian valuer.s ability to comply with the IFRS standard keeps rising every day, not just to the accountants, but also other related parties such as financial institutions, government agencies and the clients. This is happening because of different interpretations of premise of value for plant and machinery, as well as methods been used and differences in standards of reporting among the valuers conducting plant and machinery valuation. The root of the problem lies in the lack of practical guidelines governing plant and machinery valuation practices and different schools of thought among the valuers. Some follow the United Kingdom.s RICS guidelines, whilst some valuers are more comfortable with the United State.s USPAP rules, especially on the premise of value. This research is to investigate the international best practices of plant and machinery valuation and to establish the common valuation concept, awareness and application of valuation methodology and valuation process for plant and machinery valuation in Malaysia. This research uses a combination of the qualitative and quantitative research approach. In the qualitative approach, the content analyses were conducted from the international practices and current Malaysian implementation of plant and machinery valuation. A survey (quantitative approach) via questionnaire was implemented among the registered and probationary valuers in Malaysia to investigate their understanding and opinion relating to plant and machinery valuation based on the current practices. The significance of this research is the identification of international plant and machinery practices and the understanding of current practices of plant and machinery valuation in Malaysia. It is found that issues embedding plant and machinery valuation practices are limited numbers of resources available either from scholars or practitioner. This is supported by the general finding from the research survey that indicates that there are immediate needs for practical notes or guidelines to be developed and implemented to support the Malaysian valuers practising plant and machinery valuation. This move will lead to a better understanding of plant and machinery valuation, reducing discrepancies in valuation of plant and machinery and increased accuracy among practising valuers.

Genetic improvement of giant freshwater prawn in Vietnam

The giant freshwater prawn (Macrobrachium rosenbergii) or GFP is one of the most important freshwater crustacean species in the inland aquaculture sector of many tropical and subtropical countries. Since the 1990’s, there has been rapid global expansion of freshwater prawn farming, especially in Asian countries, with an average annual rate of increase of 48% between 1999 and 2001 (New, 2005). In Vietnam, GFP is cultured in a variety of culture systems, typically in integrated or rotational rice-prawn culture (Phuong et al., 2006) and has become one of the most common farmed aquatic species in the country, due to its ability to grow rapidly and to attract high market price and high demand. Despite potential for expanded production, sustainability of freshwater prawn farming in the region is currently threatened by low production efficiency and vulnerability of farmed stocks to disease. Commercial large scale and small scale GFP farms in Vietnam have experienced relatively low stock productivity, large size and weight variation, a low proportion of edible meat (large head to body ratio), scarcity of good quality seed stock. The current situation highlights the need for a systematic stock improvement program for GFP in Vietnam aimed at improving economically important traits in this species. This study reports on the breeding program for fast growth employing combined (between and within) family selection in giant freshwater prawn in Vietnam. The base population was synthesized using a complete diallel cross including 9 crosses from two local stocks (DN and MK strains) and a third exotic stock (Malaysian strain - MY). In the next three selection generations, matings were conducted between genetically unrelated brood stock to produce full-sib and (paternal) half-sib families. All families were produced and reared separately until juveniles in each family were tagged as a batch using visible implant elastomer (VIE) at a body size of approximately 2 g. After tags were verified, 60 to 120 juveniles chosen randomly from each family were released into two common earthen ponds of 3,500 m2 pond for a grow-out period of 16 to 18 weeks. Selection applied at harvest on body weight was a combined (between and within) family selection approach. 81, 89, 96 and 114 families were produced for the Selection line in the F0, F1, F2 and F3 generations, respectively. In addition to the Selection line, 17 to 42 families were produced for the Control group in each generation. Results reported here are based on a data set consisting of 18,387 body and 1,730 carcass records, as well as full pedigree information collected over four generations. Variance and covariance components were estimated by restricted maximum likelihood fitting a multi-trait animal model. Experiments assessed performance of VIE tags in juvenile GFP of different size classes and individuals tagged with different numbers of tags showed that juvenile GFP at 2 g were of suitable size for VIE tags with no negative effects evident on growth or survival. Tag retention rates were above 97.8% and tag readability rates were 100% with a correct assignment rate of 95% through to mature animal size of up to 170 g. Across generations, estimates of heritability for body traits (body weight, body length, cephalothorax length, abdominal length, cephalothorax width and abdominal width) and carcass weight traits (abdominal weight, skeleton-off weight and telson-off weight) were moderate and ranged from 0.14 to 0.19 and 0.17 to 0.21, respectively. Body trait heritabilities estimated for females were significantly higher than for males whereas carcass weight trait heritabilities estimated for females and males were not significantly different (P > 0.05). Maternal and common environmental effects for body traits accounted for 4 to 5% of the total variance and were greater in females (7 to 10%) than in males (4 to 5%). Genetic correlations among body traits were generally high in both sexes. Genetic correlations between body and carcass weight traits were also high in the mixed sexes. Average selection response (% per generation) for body weight (transformed to square root) estimated as the difference between the Selection and the Control group was 7.4% calculated from least squares means (LSMs), 7.0% from estimated breeding values (EBVs) and 4.4% calculated from EBVs between two consecutive generations. Favourable correlated selection responses (estimated from LSMs) were detected for other body traits (12.1%, 14.5%, 10.4%, 15.5% and 13.3% for body length, cephalothorax length, abdominal length, cephalothorax width and abdominal width, respectively) over three selection generations. Data in the second selection generation showed positive correlated responses for carcass weight traits (8.8%, 8.6% and 8.8% for abdominal weight, skeleton-off weight and telson-off weight, respectively). Data in the third selection generation showed that heritability for body traits were moderate and ranged from 0.06 to 0.11 and 0.11 to 0.22 at weeks 10 and 18, respectively. Body trait heritabilities estimated at week 10 were not significantly lower than at week 18. Genetic correlations between body traits within age and genetic correlations for body traits between ages were generally high. Overall our results suggest that growth rate responds well to the application of family selection and carcass weight traits can also be improved in parallel, using this approach. Moreover, selection for high growth rate in GFP can be undertaken successfully before full market size has been reached. The outcome of this study was production of an improved culture strain of GFP for the Vietnamese culture industry that will be trialed in real farm production environments to confirm the genetic gains identified in the experimental stock improvement program.

Error and uncertainty of adult age estimation of the pubic symphysis in an Australian sub-population using computed tomography

After attending this presentation, attendees will gain awareness of: (1) the error and uncertainty associated with the application of the Suchey-Brooks (S-B) method of age estimation of the pubic symphysis to a contemporary Australian population; (2) the implications of sexual dimorphism and bilateral asymmetry of the pubic symphysis through preliminary geometric morphometric assessment; and (3) the value of three-dimensional (3D) autopsy data acquisition for creating forensic anthropological standards. This presentation will impact the forensic science community by demonstrating that, in the absence of demographically sound skeletal collections, post-mortem autopsy data provides an exciting platform for the construction of large contemporary ‘virtual osteological libraries’ for which forensic anthropological research can be conducted on Australian individuals. More specifically, this study assesses the applicability and accuracy of the S-B method to a contemporary adult population in Queensland, Australia, and using a geometric morphometric approach, provides an insight to the age-related degeneration of the pubic symphysis. Despite the prominent use of the Suchey-Brooks (1990) method of age estimation in forensic anthropological practice, it is subject to intrinsic limitations, with reports of differential inter-population error rates between geographical locations1-4. Australian forensic anthropology is constrained by a paucity of population specific standards due to a lack of repositories of documented skeletons. Consequently, in Australian casework proceedings, standards constructed from predominately American reference samples are applied to establish a biological profile. In the global era of terrorism and natural disasters, more specific population standards are required to improve the efficiency of medico-legal death investigation in Queensland. The sample comprises multi-slice computed tomography (MSCT) scans of the pubic symphysis (slice thickness: 0.5mm, overlap: 0.1mm) on 195 individuals of caucasian ethnicity aged 15-70 years. Volume rendering reconstruction of the symphyseal surface was conducted in Amira® (v.4.1) and quantitative analyses in Rapidform® XOS. The sample was divided into ten-year age sub-sets (eg. 15-24) with a final sub-set of 65-70 years. Error with respect to the method’s assigned means were analysed on the basis of bias (directionality of error), inaccuracy (magnitude of error) and percentage correct classification of left and right symphyseal surfaces. Morphometric variables including surface area, circumference, maximum height and width of the symphyseal surface and micro-architectural assessment of cortical and trabecular bone composition were quantified using novel automated engineering software capabilities. The results of this study demonstrated correct age classification utilizing the mean and standard deviations of each phase of the S-B method of 80.02% and 86.18% in Australian males and females, respectively. Application of the S-B method resulted in positive biases and mean inaccuracies of 7.24 (±6.56) years for individuals less than 55 years of age, compared to negative biases and mean inaccuracies of 5.89 (±3.90) years for individuals greater than 55 years of age. Statistically significant differences between chronological and S-B mean age were demonstrated in 83.33% and 50% of the six age subsets in males and females, respectively. Asymmetry of the pubic symphysis was a frequent phenomenon with 53.33% of the Queensland population exhibiting statistically significant (χ2 - p<0.01) differential phase classification of left and right surfaces of the same individual. Directionality was found in bilateral asymmetry, with the right symphyseal faces being slightly older on average and providing more accurate estimates using the S-B method5. Morphometric analysis verified these findings, with the left surface exhibiting significantly greater circumference and surface area than the right (p<0.05). Morphometric analysis demonstrated an increase in maximum height and width of the surface with age, with most significant changes (p<0.05) occurring between the 25-34 and 55-64 year age subsets. These differences may be attributed to hormonal components linked to menopause in females and a reduction in testosterone in males. Micro-architectural analysis demonstrated degradation of cortical composition with age, with differential bone resorption between the medial, ventral and dorsal surfaces of the pubic symphysis. This study recommends that the S-B method be applied with caution in medico-legal death investigations of unknown skeletal remains in Queensland. Age estimation will always be accompanied by error; therefore this study demonstrates the potential for quantitative morphometric modelling of age related changes of the pubic symphysis as a tool for methodological refinement, providing a rigor and robust assessment to remove the subjectivity associated with current pelvic aging methods.

Determinants of contractor satisfaction

Performance in the construction industry is increasingly scrutinized as a result of the delays, cost overruns and poor quality of the industry’s products and services. Increasingly, disputes, conflicts and mismatches of objectives among participants are contributory factors. Performance measurement approaches have been developed to overcome these problems. However, these approaches focus primarily on objective measures to the exclusion of subjective measures, particularly those concerning contractor satisfaction (Co-S). The contractor satisfaction model (CoSMo) developed here is intended to rectify the situation. Data derived from a questionnaire survey of 75 large contractors in Malaysia in respect of a key project are analysed to identify participant factors and their strength of relationship with Co-S dimensions. The results are presented in the form of eight regression equations. The outcome is a tool for use by project participants to provide a better understanding of how they, and the project, affect contractor satisfaction. The developed model sheds some light on a hitherto unknown aspect of construction management in providing an increased awareness of the importance of major Malaysian construction contractors’ needs in the execution of successful projects.

Circulating microRNAs involved in multiple sclerosis

Multiple sclerosis (MS) is an immune-mediated, demyelinating and neurodegenerative disease of the central nervous system. After traumatic brain injury, it is the leading cause of neurology disability in young adults. Considerable advances have been made in identifying genes involved in MS but the genetic and phenotypic complexity associated with this disease significantly hinders any progress. A novel class of small RNA molecules, microRNAs (miRNAs) has acquired much attention because they regulate the expression of up to 30% of protein-coding genes and may play a pivotal role in the development of many, if not all, complex diseases. Seven published studies investigated miRNAs from peripheral blood mononuclear cells, CD4+, CD8+ T cell, B lymphocytes, peripheral blood leukocytes, whole blood and brain astrocytes with MS risk. The absence of MS studies investigating plasma miRNA prompted the current investigation of identifying a circulating miRNA signature in MS. We conducted a microarray analysis of over 900 known miRNA transcripts from plasma samples collected from four MS individuals and four sex-aged and ethnicity matched healthy controls. We identified six plasma miRNA (miR-614, miR-572, miR-648, miR-1826, miR-422a and miR-22) that were significantly up-regulated and one plasma miRNA (miR-1979) that was significantly down-regulated in MS individuals. Both miR-422a and miR-22 have previously been implicated in MS. The present study is the first to show a circulating miRNA signature involved in MS that could serve as a potential prognostic and diagnostic biomarker for MS.

Knowledge based urban development lessons from a non-western country : the Malaysia experience

Knowledge based urban development (KBUD) is seen as a new paradigm in urban planning and development which is now being implemented across the globe in order to increase the competitiveness of cities and regions. The KBUD concept has been widely applied in western and more developed countries over the last decade, and many have been proven successful. This paper, however, aims to provide an overview of the KBUD exercise in a context of a non western country scenario—Malaysia. Literature suggests that the urban development process in non western countries is different and very much focusing on physical elements. Whether this is the case or otherwise, this paper scrutinises the project of Multimedia Super Corridor (MSC), Malaysia, which is regarded as one of the first large scale manifestations of KBUD exercise in South East Asia. Based on development policies analysis and results of the interviews with the major stakeholders, this paper investigates the application of KBUD concept within the Malaysian context by examining the development and evolution of the city of Cyberjaya—the leading intelligent city of the MSC project. In the light of the literature and case findings, the paper provides recommendations and lessons learned, on the orchestration of KBUD, for other non western cities and regions that are working hard to develop KBUD strategies, strengthening their sustainable socio-spatial policies and seeking a global recognition.

Study of leukemia inhibitory factor polymorphism within an Australian multiple sclerosis population

OBJECTIVE: To examine a polymorphism within the 3' untranslated region of the leukemia inhibitory factor gene for an association with multiple sclerosis within an Australian case-control population. METHODS: A test group of 121 unrelated multiple sclerosis patients, of Caucasian origin, and 121 controls, matched for ethnicity, sex and age (+/-5 years) were included in the study. The LIF 3' UTR StuI polymorphism was genotyped by restriction fragment length polymorphism analysis. Statistical analysis of genotype and allele frequencies included Hardy-Weinberg law and conventional contingency table analysis incorporating the standard chi-squared test for independence. RESULTS: Allelic and genotype frequencies did not demonstrate a significant association between the case and control groups for the tested LIF 3' UTR StuI polymorphism. CONCLUSION: The results indicate that the LIF 3' UTR StuI polymorphism is not associated with multiple sclerosis, however we cannot exclude the hypothesis that other polymorphic alleles of LIF could be implicated in MS susceptibility.

Allelic variation investigation of the estrogen receptor within an Australian multiple sclerosis population

Multiple Sclerosis (MS) is a central nervous system (CNS) chronic inflammatory demyelinating disease leading to various neurological disabilities. The disorder is more prevalent for women with a ratio of 3:2 female to male. Objectives: To investigate variation within the estrogen receptor 1 (ESR1) polymorphism gene in an Australian MS case-control population using two intragenic restriction fragment length polymorphisms; the G594A located in exon 8 detected with the BtgI restriction enzyme and T938C located in intron 1, detected with PvuII. One hundred and ten Australian MS patients were studied, with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 110 age, sex and ethnicity matched controls were investigated as a comparative group. No significant difference in the allelic distribution frequency was found between the case and control groups for the ESR1 PvuII (P = 0.50) and Btg1 (P = 0.45) marker. Our results do not support a role for these two ESR1 markers in multiple sclerosis susceptibility, however other markers within ESR1 should not be excluded for potential involvement in the disorder.

Genetic investigation of methylenetetrahydrofolate reductase (MTHFR) and catechol-O-methyl transferase (COMT) in multiple sclerosis

Multiple sclerosis (MS) is a chronic neurological disease characterized by central nervous system (CNS) inflammation and demyelination. The C677T substitution variant in the methylenetetrahydrofolate reductase (MTHFR) gene has been associated with increased levels of circulating homocysteine and is a mild risk factor for vascular disease. Higher blood levels of homocysteine have also been reported in MS. Thus, the C677T mutation of the MTHFR gene may influence MS susceptibility. Noradrenaline, a neurotransmitter believed to play an immunosupressive role in neuroinflammatory disorders, is catabolized by catechol-O-methyl transferase (COMT). The COMT G158A substitution results in a three- to four-fold decreased activity of the COMT enzyme, which may influence CNS synaptic catecholamine breakdown and could also play a role in MS inflammation. We tested DNA from Australian MS patients and unaffected control subjects, matched for gender, age and ethnicity. Specifically, we genotyped the MTHFR C677T and the COMT G158A mutations. Genotype distributions showed that the homozygous mutant MTHFR genotype (T/T) and the COMT (H/H) genotype were slightly over-represented in the MS group (16% versus 11% and 24% versus 19%, respectively), but both variations failed to reach statistical significance (P=0.15 and P=0.32, respectively). Hence, results from the present study do not support a major role for either functional gene mutation in MS susceptibility.

Variation in the vitamin D receptor gene is associated with multiple sclerosis in an Australian population

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) resulting in accumulating neurological disability. The disorder is more prevalent at higher latitudes. To investigate VDR gene variation using three intragenic restriction fragment length polymorphisms (Apa I, Taq I and Fok I) in an Australian MS case-control population. One hundred and four Australian MS patients were studied with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 104 age-, sex-, and ethnicity-matched controls were investigated as a comparative group. Our results show a significant difference of genotype distribution frequency between the case and control groups for the functional exon 9 VDR marker Taq I (p(Gen) = 0.016) and interestingly, a stronger difference for the allelic frequency (p(All) = 0.0072). The Apa I alleles were also found to be associated with MS (p(All) = 0.04) but genotype frequencies were not significantly different from controls (p(Gen) = 0.1). The Taq and Apa variants are in very strong and significant linkage disequilibrium (D' = 0.96, P < 0.0001). The genotypic associations are strongest for the progressive forms of MS (SP-MS and PP-MS). Our results support a role for the VDR gene increasing the risk of developing multiple sclerosis, particularly the progressive clinical subtypes of MS.