Projects beginning in 1999

Identification of genetic factors that play an important role in the development of obesity

1. To determine if there is an association between peroxisome proliferator activated receptor g (PPARg), agouti-related transcript (ART), neuropeptide Y (NPY) and its receptors NPY, Y5R and Y6R, pro-opiomelanocortin (POMC), uncoupling protein 2 (UCP2), melanocortin-4 receptor (MC4R) and obesity.
2. PCR of microsatellites regions within areas of suspected linkage will be used to identify candidate gene loci using affected sib pairs.
3. Genes showing linkage will be studied for polymorphisms using denaturing gradient gel electrophoresis (DGGE) and sequencing.
4. The prevalence of each polymorphism will be studied in the obese case-control population and its association with increased BMI and CHD determined.

• Dr John Beilby, PathCentre
• Dr Caroline Chapman, PathCentre
• Dr Michael Swarbrick

Completed

Swarbrick MM, Chapman CML, McQuillan BM, Hung J, Thompson PL, Beilby JP. A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor-gamma2 is associated with combined hyperlipidaemia in obesity. Eur J Endocrinol 2001; 144: 277-82. Abstract

A case-cohort study of new risk factors for cardiovascular diseases in Busselton

The aim of this project is to conduct a case-cohort study investigating new risk factors for cardiovascular disease using baseline data, stored sera, and follow-up data that have been collected on participants in the Busselton Health Study (BHS). The new risk factors under investigation are Chlamydia pneumoniae (CP), Helicobacter pylori (HP) and Cytomegalovirus (CMV) infection, remnant-like particle cholesterol (RLP-cholesterol), homocysteine, and serum ferritin. These will be investigated in relation to both coronary heart disease (CHD) and stroke.
The hypotheses are:
• Prior CP, HP or CMV infection, indicated by the presence of IgG and IgA antibodies against these pathogens, singly and in combination, are risk factors for CHD and stroke.
• The level of serum RLP-cholesterol is an independent risk factor for coronary heart disease and stroke.
• Serum homocysteine is an independent risk factor for CHD and stroke.
• Serum ferritin is an independent risk factor for CHD and stroke.

• Prof Matthew Knuiman, School of Population Health, UWA
• Assoc Prof Gerald Watts, Dept of Medicine, UWA
• Dr Katie Coles, School of Population Health, UWA

Completed

Coles KA, Knuiman MW, Plant AJ, Riley TV, Smith DW, Divitini ML. A prospective study of infection and cardiovascular diseases: the Busselton Health Study. European Journal of Cardiovascular Prevention and Rehabilitation 2003; 10:278-282. Abstract

Knuiman MW, Divitini ML, Olynyk JK, Cullen DJE, Bartholomew HC. Serum ferritin and cardiovascular disease: a 17-year follow-up study in Busselton, Western Australia. American Journal of Epidemiology 2003; 158:144-149. Abstract

Knuiman MW, Watts GF, Divitini ML. Is sialic acid an independent risk factor for cardiovascular disease? A 17-year follow-up study in Busselton, Western Australia. Annals of Epidemiology 2004; 14(9):627-32. Abstract

O'Leary CM, Knuiman MW, Divitini ML. Homocysteine and cardiovascular disease: A 17-year followup study in Busselton. European Journal of Cardiovascular Prevention and Rehabilitation 2004; 11(4):350-1. Abstract

Continuing epidemiological analyses of respiratory diseases in Busselton.

The aim of this project is to investigate epidemiological aspects of respiratory conditions using repeated cross-sectional and follow-up data collected over the period 1966 to 2000 on participants in surveys in Busselton, Western Australia. The proposed analyses build on previous successful research on respiratory diseases in Busselton. The research topics and the specific hypotheses are:
Increasing prevalence of asthma
(a) The observed increasing prevalence of asthma parallels increases in wheeze and hayfever but there were no parallel increases in atopy or airway responsiveness.
(b) The observed increasing prevalence in asthma in adults is more pronounced in those under 40 years of age, cannot be explained by particular (birth) cohort effects, and is only partly explained by changes in diagnosis patterns.
Decline in lung function and COPD
(a) Decline in lung function (obtained from repeated measurement in individuals) is an additional useful marker of lung health beyond a single FEV1 measure (even if expressed as a percent of predicted normal value based on age and height).
(b) Decline in lung function during adulthood accelerates with increasing age.
(c) Decline in lung function is associated with peak FEV1, airway responsiveness, asthma, smoking, respiratory symptoms, atopy, cardiovascular disease, white cell count, and birth cohort.
(d) Age, lung function, asthma, smoking and respiratory symptoms are predictive of development of COPD.
Snoring and sleep apnoea
(a) Overweight, recent weight gain, upper airway dimensions, smoking, heavy alcohol intake, respiratory illness, cardiovascular disease and the use of sedative medications are risk factors for snoring and sleep apnoea.
(b) The effects overweight, weight gain and upper airway dimensions have stronger associations with snoring and sleep apnoea in women.
(c) Snoring is an independent risk factor for hypertension.
Passive smoking (spousal)
(a) The decline in husband-wife correlation in lung function with increasing marriage duration will be explained (or even reversed) after controlling for smoking habits, asthma and respiratory symptom.
(b) Passive smoking (via spouse) will be a significantly related to respiratory events, lung function and decline in lung function in non-smoking spouses of individuals who smoke.

• Prof Matthew Knuiman, School of Population Health, UWA
• Clin Prof Bill Musk, Dept of Respiratory Medicine, SCGH
• Dr Alan James, Dept of Pulmonary Physiology, SCGH
• Dr Gerry Ryan, Dept of Medicine, UWA

In progess

Knuiman MW, Divitini ML, Bartholomew HC. Spouse selection and environmental effects on spouse correlation in lung function measures. Annals of Epidemiology 2005; 15: 39-43. Abstract

Knuiman MW, James AL, Divitini ML, Bartholomew HC. Correlates of habitual snoring and witnessed apnoeas in Busselton, Western Australia. Aust NZ J Public Health 2005; 29: 412-15.

James AL, Palmer LJ, Kicic E, Maxwell PS, Lagan SE, Ryan GF, Musk AW. Decline in lung function in the Busselton Health Study: the effects of asthma and cigarette smoking. Am J Resp Crit Care Med 2004; 171: 109-14. Abstract

James AL, Knuiman MW, Bartholomew HC, Musk AW. What can Busselton tell us about asthma in the elderly?. Med J Aust 2005; 183(1 Suppl): S17-S19.

Impact of Busselton Health Studies on cardiovascular mortality and morbidity rates

1. To gather population, mortality and hospital morbidity data for the Shire of Busselton and the South-West of Western Australia.
2. To evaluate the impact of the Busselton Health Study program of activities on cardiovascular mortality rates over the period 1965-1998 in the Shire of Busselton by comparison with the remainder of the South-West of WA.
3. To see if the gender-difference in the impact on cardiovascular mortality rates observed in an earlier mortality evaluation has continued.
4. To evaluate the impact of the Busselton Health Study program of activities on cardiovascular hospital admission rates over the period 1975-1997 in the Shire of Busselton by comparison with the remainder of the South-West of WA.
5. To communicate the findings of this evaluation back to the Busselton community and to disseminate the findings more widely in a peer-reviewed journal.

• Prof Matthew Knuiman, School of Population Health, UWA
• Dr Jo Clarkson, School of Population Health, UWA

Completed

Knuiman MW, Clarkson JP, Bulsara MK, Bartholomew HC. Evaluating the impact of repeated community-wide health surveys on cardiovascular morbidity and mortality in the Busselton population. Aust NZ J Public Health 2004; 28: 267-72. Abstract

Cardiovascular disease risk factors in the elderly

1. To measure, compare and contrast risk factor-CVD associations in independent cohorts of middle-aged and elderly people, and thereby to ascertain the suitability of risk scoring systems developed from middle-aged cohorts for use in elderly cohorts. The risk factors considered will include plasma glucose and C-reactive protein as well as a measure of the metabolic syndrome.

2. To use repeated measures of risk factors in individuals over periods of 5 to 25 years to track risk factor measures into old age and to determine the relative predictive power of risk factor values measured at various ages.

3. To compare the predictive power of risk factors in people with and without existing CVD, and to incorporate the predictive power of CVD history, co-morbidity, surgical interventions and drug therapy into scoring systems.

4. To develop and validate new multivariate CVD risk assessment methods for use in contemporary elderly Australians for people with and without pre-existing cardiovascular disease.

• Prof Matthew Knuiman, School of Population Health, UWA
• Assoc Prof Joseph Hung, School of Medicine and Pharmacology, UWA
• Prof Tim Davis, School of Medicine and Pharmacology, UWA
• Dr John Beilby, Department of Clinical Biochemistry, PathCentre

In progress

Meta-analysis of rheological factors and coronary heart disease

• Dr John Danesh, PSC collaboration
• Prof Rory Collins, PSC collaboration
• Prof Richard Peto, PSC collaboration
• Dr Gordon Lowe, PSC collaboration

Completed

Danesh J, Collins R, Peto R, Lowe GD. Haematocrit, viscosity, erythrocyte sedimentation rate: meta-analyses of prospective studies of coronary heart disease. Eur Heart J 2000; 21: 515-20.

The prevalence of coeliac disease and investigation of iron deficiency in a normal community cohort

Aim 1: Measure the prevalence of Coeliac Disease in an Australian community, by using serum anti-endomysial antibodies as a screening test, and proceeding to endoscopic duodenal biopsy n those who are positive. In those who are diagnosed with Coeliac Disease we will be able to analyse data regarding Body Mass Index, history of fractures and incidence of diabetes to address whether any of these are correlates, as has been reported in other population studies.
Aim 2: Measure the prevalence of Coeliac Disease in a group who have been recognised as being iron-deficient. By comparing to age- and gender-matched controls, a relative risk of having Coeliac Disease if iron deficient will be estimated.
Aim 3: Provide information regarding the natural history of iron deficiency in a non-hospitalised population, by performing follow-up studies 5 years after the bloods were taken.
Our hypothesis is that the true prevalence of Coeliac Disease in an otherwise healthy Australian population is much higher than previous estimates quoted in the literature, which have mainly been arrived at through case acquisition. We also hypothesise that it will be an important causative factor in those subjects with persistent iron deficiency.
The significance of this study is that if Coeliac Disease is indeed more common in our community than currently appreciated, it is important to raise community and doctor awareness of this, because it is so easily treated, and successful treatment can avoid potential complications such as anaemia, ostopenia and also the small but increased risk of malignancy.

• Dr Judith Collett, Dept of Gastroenterology, Fremantle Hospital
• Dr Digby Cullen, Dept of Gastroenterology, Fremantle Hospital
• Dr Chris Hovell, Dept of Gastroenterology, Fremantle Hospital
• Dr D F Mallon, Dept of Immunology, Fremantle Hospital
• Adrian Griffiths, Dept of Gastroenterology, Fremantle Hospital

In progress

Hovell CJ, Collett JA, Vautier G, Cheng AJP, Sutanto E, Mallon D, Olynyk JK, Cullen DJE. High prevalence of coeliac disease in the Busselton population: a case for screening?. MJA 2001; 175: 247-250. Abstract

A proposed study of the prevalence and predictive value of thyroid peroxidase antibodies in the Busselton population

1. Assess the prevalence of TPO antibodies in an unselected population of men and women
2. Determine the age-specific predictive value of the TPO antibody measurement in the development of thyroid dysfunction

• Assoc Prof Peter Leedman, Dept of Medicine, UWA
• Dr Joey Kaye, Dept of Endocrinology and Diabetes, Royal Perth Hospital
• Dr Peter O'Leary, Clinical Pathology and Biochemistry, RPH
• Peter Feddema, Bio-Mediq-DPC
• Dr Valdo Michelangeli, Bio-Mediq-DPC
• Dr Peter Hollingsworth, Dept of Clinical Immunology, PathCentre

In progress

O'Leary PC, Feddema PH, Michelangeli VP, Leedman PJ, Chew GT, Knuiman M, Kaye J, Walsh JP. Investigations of thyroid hormones and antibodies based on a community health survey: the Busselton thyroid study. Clin Endocrinol (Oxf) 2006; 64(1):97-104.

Tracking Helicobacter pylori transmission between spouses.

To isolate and to type H. pylori isolates from infected couples

• Prof Barry Marshall, Dept of Medicine, UWA

Completed

The association between cardiovascular disease and genetic haemochromatosis: a population based study

The aims of the porposed study would be to look at the association of cardiovascular disease with those patients previously found to have either a) a raised serum ferritin, b) a raised serum transferrin saturation or c) genotypes C282Y/C282Y, C282Y/wt and C282Y/H63D.

• Dr Chris Hovell, Dept of Gastroenterology, Fremantle Hospital
• Dr K Patel, Dept of Gastroenterology, Fremantle Hospital
• Prof John Olynyk, Dept of Gastroenterology, Fremantle Hospital
• Prof Matthew Knuiman, School of Population Health, UWA
• Dr Ric Rossi, PathCentre
• Prof Lawrie Powell, Queensland Institute of Medical Research
• Dr Digby Cullen, Dept of Gastroenterology, Fremantle Hospital

Completed

Fox CJ, Cullen DJE, Knuiman MW, Cumpston NG, Divitini ML, Rossi E, Gochee PA, Powell LW, Olynyk JK. Effects of body iron stores and haemochromatosis genotypes on coronary heart disease outcomes in the Busselton Health Study. Journal of Cardiovascular Risk 2002; 9: 287-293. Abstract