Is CEO human capital related to firm performance?

The global economy experienced continuous growth from 2002 to 2007 until the U.S. subprime mortgage crisis caused instability in worldwide stock markets. Simultaneously, global CEO turnover continued to fall to 13.8 percent in 2007. In contrast, the CEO turnover rate in Australia increased to 18 percent in 2007. The purpose of this paper is to determine under what conditions a change in a CEO is associated with firm performance. Succinctly, does the firm’s decision to replace the CEO depend on the CEO’s human capital or firm performance? The empirical study of Australian listed firms (2005 – 2008) shows that firm performance is not a determinant of CEO turnover, rather a CEO with less valuable human capital is more likely to be replaced. The study also finds that merely changing the CEO is not associated firm performance. Rather, there is a positive association between firm performance and the successor’s general human capital for firms that replace the CEO. Specifically, it is the internal successor’s general human capital that is an important determinant of increasing firm performance. These results are important because they imply that CEO turnover is a result of a more active market for CEOs and contributes to explaining why firms retain CEOs despite poor firm performance.

"I drove after drinking alcohol" and other risky driving behaviours reported by young novice drivers

Background Volitional risky driving behaviours including drink- and drug-driving and speeding contribute to the overrepresentation of young novice drivers in road crash fatalities, and crash risk is greatest during the first year of independent driving in particular. Aims To compare: 1) the self-reported compliance of drivers with road rules relating to substance-impaired driving and other risky driving behaviours including speeding and driving tired, one year after progression from a Learner to a Provisional (intermediate) licence; and 2) the interrelationships between substance-impaired driving and other risky driving behaviours (crashes, offences, and Police avoidance). Methods 1268 drivers (373 males) aged 17-26 years were surveyed regarding their sociodemographics (age, gender) and self-reported driving behaviours including crashes, offences, Police-avoidance, and driving intentions. Results A relatively small proportion of participants reported driving after taking drugs (5.9% males, 1.3% females) and drinking alcohol (19.3% males, 11.6% females). In comparison, a considerable proportion of participants reported at least occasionally exceeding speed limits (85.7% novices) and driving when tired (82.7% novices). Substance-impaired driving was associated with avoiding Police, speeding, risky driving intentions, and self reported crashes and offences. Forty-four percent of illicit-drug drivers also reported alcohol-impaired driving. Discussion and conclusions The low self-reported prevalence of substance-impaired driving suggests official enforcement measures play a role in promoting compliance, in addition to social influences such as the broader community and the young novice drivers’ social networks including friends and family. Conversely, the prevalence of speeding appears to reflect the pervasive cultural acceptance of this behaviour. Given the interrelationships between the risky driving behaviours, a deeper understanding of influential factors is required to inform targeted and general countermeasure implementation and evaluation during this critical driving period.

Identifying and using ehealth phobias to implement communication protocols and change cultural and social behaviours in ehealth

Standardisation of validated communication protocols that aid in the adoption of policies, methods and tools in a secure eHealth setting require a significant cultural shift among clinicians

A systematic review of the literature comparing the practices of dispensing and non-dispensing doctors

Objectives: Some doctors perform the dual roles of prescribing and dispensing pharmaceuticals. The dispensing doctors (DDs) role may give rise to prescribing behaviours that vary from those of non-DDs. The aim of this review was to systematically and comparatively appraise the research evidence related to the practices of DDs. Methods: A systematic search of bibliographic databases and reference lists from selected papers were the sources of the data. Inclusion criteria were papers published in English, between 1970 and 2008 that provided quantitative data comparing the practices of DDs and non-DDs. At least two of the authors abstracted data from all eligible papers using a purpose-made data extraction form. Results: Twenty-one papers were included in this review. Evidence indicated that DDs prescribed more pharmaceutical items and less often generically than non-DDs. There was limited evidence to suggest that DDs prescribed less judiciously and were associated with poor dispensing standards. Patient convenience and access to pharmaceuticals were main reasons for doctors to dispense. Conclusion: DDs can fill an important gap in the provision of pharmaceuticals for their patients especially where health workforce shortages exist. There was evidence the dispensing role influenced prescribing. Patient convenience should be balanced against scarce medical resources, being utilised for dispensing.

Cryptic diversity and evolutionary relationships among Australian closed-forest Melomys (Rodentia: Muridae) and related Australo-Papuan mosaic-tailed rats

This thesis investigates patterns of evolution in a group of native Australo-Papuan rodents. Past climatic change and associated sea level fluctuations, and fragmentation of wet forests in eastern Australia has facilitated rapid radiation, diversification and speciation in this group. This study adds to our understanding of the evolution of Australia’s rainforest fauna and describes the evolutionary relationships of a new genus of Australian rodent.

An analysis of corporate related-party disclosure in the Asia-Pacific region

Related-party (RP) transactions are said to be commonly used opportunistically in business and contribute to corporate failures. While periodic disclosure is widely accepted as an effective means of monitoring such transactions, research is scant, particularly in countries where business dealings may be more susceptible to corruption. This study investigates the nature and extent of corporate RP disclosures across six countries in the Asia-Pacific region. The key finding indicates that companies in countries with stronger regulatory enforcement, shareholders’ protection, and control for corruption, have more transparent RP disclosures. This evidence potentially contributes to reforms aimed at strengthening RP disclosure and compliance.

Studies of the off-field behaviours of sportspeople : are sponsors' objectives at risk?

The research reported here addresses the problem of athlete off-field behaviours as they influence sports’ sponsors, particularly the achievement of sponsorship objectives. The question arises because of incidents of sponsorship contract cancellation following news-media reporting of athletes’ off-field behaviours. Two studies are used to investigate the research question; the first establishes the content of news-media reports, and the second tests the effects of news’ reports on athlete, team and sponsor evaluations using an experimental design. Key assumptions of the research are that sponsorship objectives are principally consumer-based and mediated. Models of sponsorship argue that sponsors aim to reach and influence consumers through sponsees. Assuming this pathway exists is central to sponsorship activities. A corollary is that other mediators, in this case the news-media, may also communicate (uncontrollable) messages such that a consumer audience may be told of negative news that may then be associated with the sponsor. When sponsors cancel contracts it is assumed that their goal is to control the links between their brand and a negative referent. Balance theory is used to discuss the potential effects of negative off-field behaviours of athletes on sponsor’s objectives. Heider’s balance theory (1958) explains that individuals prefer to evaluate linked individuals or entities consistently. In the sponsorship context this presents the possibility that a negative evaluation of the athlete’s behaviour will contribute to correspondingly negative evaluations of the athlete’s team and sponsors. A content analysis (Study 1) was used to survey the types of athlete off-field behaviours commonly reported in a newspaper. In order to provide a local context for the research, articles from the Courier Mail were sampled and teams in the National Rugby League (NRL) competition were the focus of the research. The study identified nearly 2000 articles referring to the NRL competition; 258 of those refer to off-field incidents involving athletes. The various types of behaviours reported include assault, sexual assault allegations, driving under the influence of alcohol, illicit drug use, breaches of club rules, and positive off-field activities (i.e., charitable activities). An experiment (Study 2) tested three news’ article stimuli developed from the behaviours identified in Study 1 in a between-subjects design. A measure of Identification with the Team was used as a covariate variable in the Multivariate Analysis of Covariance analysis. Social identity theory suggests that when an individual identifies with a group, their attitudes and behaviours towards both in- and out-group members are modified. Use of Identification with the Team as a covariate acknowledges that respondents will evaluate behaviours differently according to the attribution of those behaviours to an in- or out-group member. Findings of the research suggest that the news’ article stimuli have significant, large effects on evaluations of athlete off-field behaviour and athlete Likability. Consistent with pretest results, charitable fundraising is regarded as extremely positive; the athlete, correspondingly, is likable. Assault is evaluated as extremely negative, and the athlete as unlikable. DUI scores reveal that the athlete’s behaviour is very negative; however, the athlete’s likability was evaluated as neutral. Treatment group does not produce any significant effects on team or sponsor variables. This research also finds that Identification with the Team has significant, large effects on team variables (Attitude toward the Brand and Corporate Image). Identification also has a significant large effect on athlete Likability, but not on Attitude toward the Act. Identification with the Team does not produce any significant effects on sponsor variables. The results of this research suggest that sponsor’s consumer-based objectives are not threatened by newspaper reports linking athlete off-field behaviour with their brand. Evaluations of sponsor variables (Attitude toward the Sponsor’s Brand and Corporate Image) were consistently positive. Variance in that data, however, cannot be attributed to experimental stimuli or Identification with the Team. These results argue that respondents may regard sponsorships, in principle, as good. Although it is good news for sponsors that negative evaluations of athletes will not produce correspondingly negative evaluations of consumer-based sponsorship objectives, the results indicate problems for sponsorship managers. The failure of Identification with the Team to explain sponsor variable variance indicates that the sponsor has not been evaluated as a linked entity in a relationship with the sporting team and athlete in this research. This result argues that the sponsee-mediated affective communication path that sponsors aim use to communicate with desirable publics is not necessarily a path available to them.

The individual and interactive relationship between long chain omega-3 polyunsaturated fatty acids and physical activity as predictors of cognition in cognitively impaired and non-impaired older adults

Alterations in cognitive function are characteristic of the aging process in humans and other animals. However, the nature of these age related changes in cognition is complex and is likely to be influenced by interactions between genetic predispositions and environmental factors resulting in dynamic fluctuations within and between individuals. These inter and intra-individual fluctuations are evident in both so-called normal cognitive aging and at the onset of cognitive pathology. Mild Cognitive Impairment (MCI), thought to be a prodromal phase of dementia, represents perhaps the final opportunity to mitigate cognitive declines that may lead to terminal conditions such as dementia. The prognosis for people with MCI is mixed with the evidence suggesting that many will remain stable within 10-years of diagnosis, many will improve, and many will transition to dementia. If the characteristics of people who do not progress to dementia from MCI can be identified and replicated in others it may be possible to reduce or delay dementia onset, thus reducing a growing personal and public health burden. Furthermore, if MCI onset can be prevented or delayed, the burden of cognitive decline in aging populations worldwide may be reduced. A cognitive domain that is sensitive to the effects of advancing age, and declines in which have been shown to presage the onset of dementia in MCI patients, is executive function. Moreover, environmental factors such as diet and physical activity have been shown to affect performance on tests of executive function. For example, improvements in executive function have been demonstrated as a result of increased aerobic and anaerobic physical activity and, although the evidence is not as strong, findings from dietary interventions suggest certain nutrients may preserve or improve executive functions in old age. These encouraging findings have been demonstrated in older adults with MCI and their non-impaired peers. However, there are some gaps in the literature that need to be addressed. For example, little is known about the effect on cognition of an interaction between diet and physical activity. Both are important contributors to health and wellbeing, and a growing body of evidence attests to their importance in mental and cognitive health in aging individuals. Yet physical activity and diet are rarely considered together in the context of cognitive function. There is also little known about potential underlying biological mechanisms that might explain the physical activity/diet/cognition relationship. The first aim of this program of research was to examine the individual and interactive role of physical activity and diet, specifically long chain polyunsaturated fatty acid consumption(LCn3) as predictors of MCI status. The second aim is to examine executive function in MCI in the context of the individual and interactive effects of physical activity and LCn3.. A third aim was to explore the role of immune and endocrine system biomarkers as possible mediators in the relationship between LCn3, physical activity and cognition. Study 1a was a cross-sectional analysis of MCI status as a function of erythrocyte proportions of an interaction between physical activity and LCn3. The marine based LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both received support in the literature as having cognitive benefits, although comparisons of the relative benefits of EPA or DHA, particularly in relation to the aetiology of MCI, are rare. Furthermore, a limited amount of research has examined the cognitive benefits of physical activity in terms of MCI onset. No studies have examined the potential interactive benefits of physical activity and either EPA or DHA. Eighty-four male and female adults aged 65 to 87 years, 50 with MCI and 34 without, participated in Study 1a. A logistic binary regression was conducted with MCI status as a dependent variable, and the individual and interactive relationships between physical activity and either EPA or DHA as predictors. Physical activity was measured using a questionnaire and specific physical activity categories were weighted according to the metabolic equivalents (METs) of each activity to create a physical activity intensity index (PAI). A significant relationship was identified between MCI outcome and the interaction between the PAI and EPA; participants with a higher PAI and higher erythrocyte proportions of EPA were more likely to be classified as non-MCI than their less active peers with less EPA. Study 1b was a randomised control trial using the participants from Study 1a who were identified with MCI. Given the importance of executive function as a determinant of progression to more severe forms of cognitive impairment and dementia, Study 1b aimed to examine the individual and interactive effect of physical activity and supplementation with either EPA or DHA on executive function in a sample of older adults with MCI. Fifty male and female participants were randomly allocated to supplementation groups to receive 6-months of supplementation with EPA, or DHA, or linoleic acid (LA), a long chain polyunsaturated omega-6 fatty acid not known for its cognitive enhancing properties. Physical activity was measured using the PAI from Study 1a at baseline and follow-up. Executive function was measured using five tests thought to measure different executive function domains. Erythrocyte proportions of EPA and DHA were higher at follow-up; however, PAI was not significantly different. There was also a significant improvement in three of the five executive function tests at follow-up. However, regression analyses revealed that none of the variance in executive function at follow-up was predicted by EPA, DHA, PAI, the EPA by PAI interaction, or the DHA by PAI interaction. The absence of an effect may be due to a small sample resulting in limited power to find an effect, the lack of change in physical activity over time in terms of volume and/or intensity, or a combination of both reduced power and no change in physical activity. Study 2a was a cross-sectional study using cognitively unimpaired older adults to examine the individual and interactive effects of LCn3 and PAI on executive function. Several possible explanations for the absence of an effect were identified. From this consideration of alternative explanations it was hypothesised that post-onset interventions with LCn3 either alone or in interation with self-reported physical activity may not be beneficial in MCI. Thus executive function responses to the individual and interactive effects of physical activity and LCn3 were examined in a sample of older male and female adults without cognitive impairment (n = 50). A further aim of study 2a was to operationalise executive function using principal components analysis (PCA) of several executive function tests. This approach was used firstly as a data reduction technique to overcome the task impurity problem, and secondly to examine the executive function structure of the sample for evidence of de-differentiation. Two executive function components were identified as a result of the PCA (EF 1 and EF 2). However, EPA, DHA, the PAI, or the EPA by PAI or DHA by PAI interactions did not account for any variance in the executive function components in subsequent hierarchical multiple regressions. Study 2b was an exploratory correlational study designed to explore the possibility that immune and endocrine system biomarkers may act as mediators of the relationship between LCn3, PAI, the interaction between LCn3 and PAI, and executive functions. Insulin-like growth factor-1 (IGF-1), an endocrine system growth hormone, and interleukin-6 (IL-6) an immune system cytokine involved in the acute inflammatory response, have both been shown to affect cognition including executive functions. Moreover, IGF-1 and IL-6 have been shown to be antithetical in so far as chronically increased IL-6 has been associated with reduced IGF-1 levels, a relationship that has been linked to age related morbidity. Further, physical activity and LCn3 have been shown to modulate levels of both IGF-1 and IL-6. Thus, it is possible that the cognitive enhancing effects of LCn3, physical activity or their interaction are mediated by changes in the balance between IL-6 and IGF-1. Partial and non-parametric correlations were conducted in a subsample of participants from Study 2a (n = 13) to explore these relationships. Correlations of interest did not reach significance; however, the coefficients were quite large for several relationships suggesting studies with larger samples may be warranted. In summary, the current program of research found some evidence supporting an interaction between EPA, not DHA, and higher energy expenditure via physical activity in differentiating between older adults with and without MCI. However, a RCT examining executive function in older adults with MCI found no support for increasing EPA or DHA while maintaining current levels of energy expenditure. Furthermore, a cross-sectional study examining executive function in older adults without MCI found no support for better executive function performance as a function of increased EPA or DHA consumption, greater energy expenditure via physical activity or an interaction between physical activity and either EPA or DHA. Finally, an examination of endocrine and immune system biomarkers revealed promising relationships in terms of executive function in non-MCI older adults particularly with respect to LCn3 and physical activity. Taken together, these findings demonstrate a potential benefit of increasing physical activity and LCn3 consumption, particularly EPA, in mitigating the risk of developing MCI. In contrast, no support was found for a benefit to executive function as a result of increased physical activity, LCn3 consumption or an interaction between physical activity and LCn3, in participants with and without MCI. These results are discussed with reference to previous findings in the literature including possible limitations and opportunities for future research.

Are we missing opportunities? Understanding health behaviours associated with overweight in pregnancy

While maternal obesity, excess pregnancy weight gain and lifestyle behaviours are associated with future overweight for both mothers and babies, there is limited research on how best to intervene. An evidence base that identifies behavioural influences is crucial to the development of effective interventions. This thesis aims to gain an understanding of maternal behavioural outcomes of healthy eating, physical activity and gestational weight gain (GWG), the psychosocial influences on these and to examine differences according to pre-pregnancy weight status. The New Beginnings Healthy Mothers and Babies Study was a prospective observational study using the PRECEDE-PROCEED model of health promotion planning as a framework. A consecutive sample of 715 women was recruited. Height and weight were measured and women completed questionnaires at approximately 16 and 36 weeks gestation. This thesis presents three chapters of original research across four study domains. While healthy eating was widely regarded as important during pregnancy and had become more so, there was more variability in attitudes towards physical activity. Ninety-two percent of participants achieved the maximum knowledge score relating to the influence of nutrition on pregnancy. However, 8% and 36% respectively knew how many serves of fruit and vegetables should be consumed daily. Six percent of participants met the recommendations for fruit consumption, 4% achieved the recommended vegetable intake and 44% achieved sufficient physical activity. There were few differences between healthy and overweight women for measures of physical activity and healthy eating. Many predisposing, reinforcing and enabling factors with a positive influence on health behaviours were lower in women commencing pregnancy overweight and those factors with a negative influence on health behaviours were higher when compared to healthy weight women. Some of these antecedents to health behaviours that were different according to prepregnancy weight status were associated with diet quality and physical activity. While self efficacy was consistently associated with diet quality and physical activity for both weight groups, other associations between specific predisposing, reinforcing and enabling factors differed with behaviour and weight status group. These results highlight the complexity of supporting behaviour change in a one-size-fits-all approach. Sixty-four percent of participants gained weight outside of recommendations. Compared to healthy weight women, those women who were already overweight at the beginning of pregnancy were more likely to gain too much weight (30% vs 56%, p<0.001). Only 35% of participants reported their correct recommended weight gain. Excess GWG was associated with few predisposing factors, however, these were not consistent between prepregnancy weight status groups. Less than 50% of women reported sometimes/usually/always receiving advice from health professionals relating to healthy eating, physical activity or GWG. These results indicate that there are opportunities to improve the advice and support provided by health care professionals in the antenatal period. Evidence from this PhD research suggests that there is a need for effective prevention and management of excess weight in pregnancy. Effective management of this problem is likely to require a multidisciplinary approach with multi-level strategies. Importantly, the strategies may need to be tailored according to pre-pregnancy weight status. Collectively, the evidence derived from this thesis suggests that opportunities to support healthy lifestyles and prevent future overweight are being missed during pregnancy.

Anthropometry and body composition of Indonesian adults : an evaluation of body image, eating behaviours, and physical activity

This thesis examines the characteristics of anthropometry and body composition in Indonesian adults and some of the risk factors including body image, eating behaviours, and physical activity. Examination on body image, eating behaviours, and physical activity demonstrates significant correlations with anthropometry and body composition in Indonesian adults. The study also identified body image distortion in some of the participants and provides suggestions for intervention development addressed to the groups of participants which have been identified as having a distorted body image.

An envirogenomic signature is associated with risk of IBD-related surgery in a population-based Crohn’s Disease cohort

BACKGROUND AND AIMS: Crohn's disease (CD) is an inflammatory bowel disease (IBD) caused by a combination of genetic, clinical, and environmental factors. Identification of CD patients at high risk of requiring surgery may assist clinicians to decide on a top-down or step-up treatment approach. METHODS: We conducted a retrospective case-control analysis of a population-based cohort of 503 CD patients. A regression-based data reduction approach was used to systematically analyse 63 genomic, clinical and environmental factors for association with IBD-related surgery as the primary outcome variable. RESULTS: A multi-factor model was identified that yielded the highest predictive accuracy for need for surgery. The factors included in the model were the NOD2 genotype (OR = 1.607, P = 2.3 × 10(-5)), having ever had perianal disease (OR = 2.847, P = 4 × 10(-6)), being post-diagnosis smokers (OR = 6.312, P = 7.4 × 10(-3)), being an ex-smoker at diagnosis (OR = 2.405, P = 1.1 × 10(-3)) and age (OR = 1.012, P = 4.4 × 10(-3)). Diagnostic testing for this multi-factor model produced an area under the curve of 0.681 (P = 1 × 10(-4)) and an odds ratio of 3.169, (95 % CI P = 1 × 10(-4)) which was higher than any factor considered independently. CONCLUSIONS: The results of this study require validation in other populations but represent a step forward in the development of more accurate prognostic tests for clinicians to prescribe the most optimal treatment approach for complicated CD patients.

Association study of the calcitonin gene-related polypeptide-alpha (CALCA) and the receptor activity modifying 1 (RAMP1) genes with migraine

Migraine is a common neurovascular brain disorder characterised by recurrent attacks of severe headache that may be accompanied by various neurological symptoms. Migraine is thought to result from activation of the trigeminovascular system followed by vasodilation of pain-producing intracranial blood vessels and activation of second-order sensory neurons in the trigeminal nucleus caudalis. Calcitonin gene-related peptide (CGRP) is a mediator of neurogenic inflammation and the most powerful vasodilating neuropeptide, and has been implicated in migraine pathophysiology. Consequently, genes involved in CGRP synthesis or CGRP receptor genes may play a role in migraine and/or increase susceptibility. This study investigates whether variants in the gene that encodes CGRP, calcitonin-related polypeptide alpha (CALCA) or in the gene that encodes a component of its receptor, receptor activity modifying protein 1 (RAMP1), are associated with migraine pathogenesis and susceptibility. The single nucleotide polymorphisms (SNPs) rs3781719 and rs145837941 in the CALCA gene, and rs3754701 and rs7590387 at the RAMP1 locus, were analysed in an Australian Caucasian population of migraineurs and matched controls. Although we find no significant association of any of the SNPs tested with migraine overall, we detected a nominally significant association (p = 0.031) of the RAMP1 rs3754701 variant in male migraine subjects, although this is non-significant after Bonferroni correction for multiple testing.

Characterisation of combustion related acoustic emission sources for diesel engine condition monitoring

This thesis represents a major step forward in understanding the link between the development of combustion related faults in diesel engines and the generation of acoustic emissions. The findings presented throughout the thesis provide a foundation so that future diesel engine monitoring systems are able to more effectively detect and monitor developing faults. In undertaking this research knowledge concerning engine function and relevant failure mechanisms was combined with different modelling methods to generate a framework that was used to effectively identify fault related activity within acoustic emissions recorded from different engines.

Perianal disease combined with NOD2 genotype predicts need for IBD-related surgery in Crohn’s Disease patients from a population-based cohort

Background: Patients with Crohn’s disease (CD) often require surgery at some stage of disease course. Prediction of CD outcome is influenced by clinical, environmental, serological, and genetic factors (eg, NOD2). Being able to identify CD patients at high risk of surgical intervention should assist clinicians to decide whether or not to prescribe early aggressive treatment with immunomodulators. Methods: We performed a retrospective analysis of selected clinical (age at diagnosis, perianal disease, active smoking) and genetic (NOD2 genotype) data obtained for a population-based CD cohort from the Canterbury Inflammatory Bowel Disease study. Logistic regression was used to identify predictors of complicated outcome in these CD patients (ie, need for inflammatory bowel disease-related surgery). Results: Perianal disease and the NOD2 genotype were the only independent factors associated with the need for surgery in this patient group (odds ratio=2.84 and 1.60, respectively). By combining the associated NOD2 genotype with perianal disease we generated a single “clinicogenetic” variable. This was strongly associated with increased risk of surgery (odds ratio=3.84, P=0.00, confidence interval, 2.28-6.46) and offered moderate predictive accuracy (positive predictive value=0.62). Approximately 1/3 of surgical outcomes in this population are attributable to the NOD2+PA variable (attributable risk=0.32). Conclusions: Knowledge of perianal disease and NOD2 genotype in patients presenting with CD may offer clinicians some decision-making utility for early diagnosis of complicated CD progression and initiating intensive treatment to avoid surgical intervention. Future studies should investigate combination effects of other genetic, clinical, and environmental factors when attempting to identify predictors of complicated CD outcomes.

Investigation of homocysteine-pathway-related variants in essential hypertension

Hyperhomocysteinemia (hHcy) has been associated with an increased risk of cardiovascular disease and stroke. Essential hypertension (EH), a polygenic condition, has also been associated with increased risk of cardiovascular related disorders. To investigate the role of the homocysteine (Hcy) metabolism pathway in hypertension we conducted a case-control association study of Hcy pathway gene variants in a cohort of Caucasian hypertensives and age- and sex-matched normotensives. We genotyped two polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR C677T and MTHFR A1298C), one polymorphism in the methionine synthase reductase gene (MTRR A66G), and one polymorphism in the methylenetetrahydrofolate dehydrogenase 1 gene (MTHFD1 G1958A) and assessed their association with hypertension using chi-square analysis. We also performed a multifactor dimensionality reduction (MDR) analysis to investigate any potential epistatic interactions among the four polymorphisms and EH. None of the four polymorphisms was significantly associated with EH and although we found a moderate synergistic interaction between MTHFR A1298C and MTRR A66G, the association of the interaction model with EH was not statistically significant (