Fine Mapping Of The ADH Region For Alcohol Metabolism, Use And Dependence
Funder
National Health and Medical Research Council
Funding Amount
$215,690.00
Summary
It is widely known that alcohol use and alcohol dependence can cause many social problems and morbidity. We know that social and and cultural factors can affect the possibility of becoming alcohol dependent. We also know that inheritance plays a major role in the risk of becoming dependent upon alcohol. Two inherited causes or genes have already been identified as causing some people to avoid alcohol and so have less chance of becoming dependent upon it. Clues as to why this happens come from wh ....It is widely known that alcohol use and alcohol dependence can cause many social problems and morbidity. We know that social and and cultural factors can affect the possibility of becoming alcohol dependent. We also know that inheritance plays a major role in the risk of becoming dependent upon alcohol. Two inherited causes or genes have already been identified as causing some people to avoid alcohol and so have less chance of becoming dependent upon it. Clues as to why this happens come from what happens to alcohol following a drink. The body detoxifies itself of alcohol in the liver. There it is converted to very highly toxic acetaldehyde and this is normally rapidly removed by a protein called aldehyde dehydrogenase. Some people do not have a normally functioning form of this protein and cannot remove the acetaldehyde from their bodies. They suffer unpleasant side effects such as nausea, facial flushing and sickness. Consequently they learn by experience to avoid alcohol use and are less likely to develop dependence. We now know that even people with a normally inherited form of aldehyde dehydrogenase can have a lowered risk of dependence. The rate at which our livers convert alcohol to actetaldehyde is also a key factor. Those who are inherently quick at this process again learn to avoid alcohol, others are more at risk. The hypothesis will be tested with a unique set of twins who have provided us with detailed information on how quickly they detoxify alcohol and of their drinking habits for over 20 years. Collectively they will enable us to determine if there is a major genetic influence on alcohol use and dependence that is caused by inter-individual differences in a gene for alcohol metabolism. The DNA of these twins will be used to locate mutations that we predict have a common effect upon our measures of alcohol detoxification, drinking habits and risk of alcoholism.Read moreRead less
The Effect Of Antiepileptic Medication On Indices Of Bone Health And Risk Factors For Falls And Fractures
Funder
National Health and Medical Research Council
Funding Amount
$469,605.00
Summary
Epilepsy is a common brain disorder and most patients with epilepsy take anti-epileptic drugs (AEDs) for many years. These patients have high rates of bone fractures, but the reasons are uncertain. Earlier studies identifying an association between AED use and bone disease were performed on institutionalised patients, and more recent studies on outpatient populations have been conflicting. A better understanding of this problem is critical for designing potential preventive measures and treatmen ....Epilepsy is a common brain disorder and most patients with epilepsy take anti-epileptic drugs (AEDs) for many years. These patients have high rates of bone fractures, but the reasons are uncertain. Earlier studies identifying an association between AED use and bone disease were performed on institutionalised patients, and more recent studies on outpatient populations have been conflicting. A better understanding of this problem is critical for designing potential preventive measures and treatments. One important additional mechanism by which AEDs may increase fracture risk is impairment of gait and balance, leading to a high risk of falls. We have novel data demonstrating the power of a Twin and Matched Sibling approach to study this important problem. This study showed that chronic AED use was associated with significant deficits in bone mineral density (BMD), a key predictor of the risk of fractures. The proposed project will ask the following questions: 1. Is BMD and estimated bone strength lower in the bones most at risk for fracture in women and men chronically taking AEDs? 2. Is the loss of bone in measurements over time greater in patients continuing to take AEDs? 3. Is the risk of bone loss greater for certain types of AEDs, and is the risk influenced by length of exposure, age and menopausal status? 4. How does AED treatment lead to reductions in BMD and bone strength? 5. Are measures of muscle strength, gait and balance impaired in patients taking AEDs compared with matched people not taking AEDs? The proposed study will utilise twins and pairs of siblings to investigate the effects of the long-term use of AEDs for epilepsy on measures of bone mass and strength, indices of bone turnover, vitamin D status, calcium regulating hormones, mineral levels, sex hormone levels, and measures of muscle strength, gait and balance function. In addition, a group of patients newly commencing AED treatment for epilepsy will be studied over 2 years.Read moreRead less