Rosienne Farrugia - Academia.edu (original) (raw)

Papers by Rosienne Farrugia

University of Malta, 2012

Ageing Research Reviews, 2022

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality in the adult popu... more Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality in the adult population worldwide and represent a severe economic burden and public health concern. The majority of human genes do not code for proteins. However, noncoding transcripts play important roles in ageing that significantly increases the risk for CVDs. Noncoding RNAs (ncRNAs) are critical regulators of multiple biological processes related to ageing such as oxidative stress, mitochondrial dysfunction and chronic inflammation. NcRNAs are also involved in pathophysiological developments within the cardiovascular system including arrhythmias, cardiac hypertrophy, fibrosis, myocardial infarction and heart failure. In this review article, we cover the roles of ncRNAs in cardiovascular ageing and disease as well as their potential therapeutic applications in CVDs.

Genotype frequencies for MTHFR, Parkinson's Disease (Table S1a) and Parkinsonism (Table S1b) ... more Genotype frequencies for MTHFR, Parkinson's Disease (Table S1a) and Parkinsonism (Table S1b) only. (DOC 57.5Â kb)

The Serotonin Transporter protein (5Hydroxytryptamine transporter; 5-HTT) is an important reuptak... more The Serotonin Transporter protein (5Hydroxytryptamine transporter; 5-HTT) is an important reuptake receptor of serotonin from the synaptic cleft. The protein is encoded by the SLC6A4 gene. A size polymorphism, the 5-HTT Linked Polymorphic Region (5-HTTLPR; SLC6A4, 44-BP INS/DEL), exists within the promoter of this gene. The presence of this polymorphism has been associated with an increased susceptibility for a variety of neurological conditions including Parkinson disease, chronic pain, anxiety and depression related phenotypes. This 5' regulatory promoter polymorphism consists of a 44–base pair insertion resulting in a long or short allele. The short allele is linked to a pronounced reduction in transcriptional efficiency producing lower numbers of transporter protein and a reduced rate of serotonin reuptake. Allele frequencies for this polymorphism show substantial variation in different populations. The frequency of the 5-HTTLPR in the population of Malta was determined in 6...

Vella, J., Borg, J., Grech, L., Galdies, R., Scerri, J., Cassar, W., Scerri, C.A., Camilleri, A.,... more Vella, J., Borg, J., Grech, L., Galdies, R., Scerri, J., Cassar, W., Scerri, C.A., Camilleri, A., Bezzina-Wettinger, S., Farrugia, R., Camilleri, G., Pace, N.P., Zammit, E., Said Conti, V., Grech, G., Saliba, C., Soler, D., Vella, N.R., Borg, I., Said, E., Camilleri Podesta, M.T., Ellul, B., Felice, T., Grima, D., Ebejer, J.P., Felice, A.E. Centre for Molecular Medicine and BioBanking, University of Malta www.um.edu.mt/biobank Contact: joanna.vella@um.edu.mt

This study aimed to determine the influence of some conventional risk factors for Myocardial Infa... more This study aimed to determine the influence of some conventional risk factors for Myocardial Infarction (MI) in the Maltese population. Some 429 cases with a first MI, 434 controls and some 190 relatives of cases have been recruited in the Maltese Acute Myocardial Infarction (MAMI) study. Data has been collected through an interviewer-led questionnaire, physical measurements and biochemistry and haematology testing. Odds ratios (OR) were calculated and adjusted (AdjOR) for age, gender, smoking/drinking alcohol, hypertension, diabetes, hypercholesterolaemia and body mass index. Smoking, diabetes, hypertension, hypercholesterolaemia and a family history of MI are amongst the risk factors associated with an increased risk of MI in the Maltese. Both active and passive smoking are associated with a 3-fold increased risk for MI. Whereas regular drinking (having at least one drink per week for one year) is associated with a decreased risk for MI [AdjOR 0.6 (95% CI 0.4-0.8], the risk associ...

Cardiovascular Research, 2021

Despite significant advances in the diagnosis and treatment of cardiovascular diseases, recent ca... more Despite significant advances in the diagnosis and treatment of cardiovascular diseases, recent calls have emphasized the unmet need to improve precision-based approaches in cardiovascular disease. Although some studies provide preliminary evidence of the diagnostic and prognostic potential of circulating coding and non-coding RNAs, the complex RNA biology and lack of standardization have hampered the translation of these markers into clinical practice. In this position paper of the CardioRNA COST action CA17129, we provide recommendations to standardize the RNA development process in order to catalyse efforts to investigate novel RNAs for clinical use. We list the unmet clinical needs in cardiovascular disease, such as the identification of high-risk patients with ischaemic heart disease or heart failure who require more intensive therapies. The advantages and pitfalls of the different sample types, including RNAs from plasma, extracellular vesicles, and whole blood, are discussed i...

Molecular Genetics and Metabolism, 2007

DeWcient activity of the Dihydropteridine Reductase enzyme (DHPR; EC 1.5.1.34; OMIM 261630) is du... more DeWcient activity of the Dihydropteridine Reductase enzyme (DHPR; EC 1.5.1.34; OMIM 261630) is due to mutations in the Quinoid Dihydropteridine Reductase gene on 4p15.3 (QDPR; RefSeq NM_000320). It results in defective recycling of tetrahydrobiopterin (BH 4) and homozygotes have a rare form of atypical Hyperphenylalaninaemia and Phenylketonuria (aPKU). The heterozygote frequency in the Maltese population is high at 3.3%. The more recently described and rarer type of BH 4 deWciency due to Sepiapterin Reductase enzyme deWciency (

Clinical genetics, 2021

The Ehlers-Danlos Syndromes (EDS) are a collection of rare hereditary connective tissue disorders... more The Ehlers-Danlos Syndromes (EDS) are a collection of rare hereditary connective tissue disorders with heterogeneous phenotypes, usually diagnosed following clinical examination and confirmatory genetic testing. Diagnosis of the commonest subtype, hypermobile Ehlers-Danlos Syndrome (hEDS), relies solely on a clinical diagnosis since its molecular aetiology remains unknown. We performed an up-to-date literature search and selected 11 out of 304 publications according to a set of established criteria. Studies reporting variants affecting collagen proteins were found to be hindered by cohort misclassification and subsequent lack of reproducibility of these genetic findings. The role of the described variants affecting Tenascin-X and LZTS1 is yet to be demonstrated in the majority of hEDS cases, while the functional implication of associated signalling pathways and genes requires further elucidation. The available literature on the genetics of hEDS is scant, dispersed and conflicting du...

In this study, DNA was extracted from whole blood which had been collected and stored at -20°C fo... more In this study, DNA was extracted from whole blood which had been collected and stored at -20°C for 5-18 years, with the aim of determining the most suitable commercial DNA extraction kit for this purpose. DNA from nine cord blood samples collected in 1999, 2001 and 2012, with low blood volumes (<1 ml), and a partly dried adult blood sample collected in 2003, having a large blood volume (6 ml) was extracted using four different DNA extraction kits: Quick-DNA Miniprep Plus kit, DNeasy Blood & Tissue kit, MagAttract HMW DNA kit and QIAamp Blood Maxi kit. We concluded that high-quality DNA can be extracted from whole blood sample collections which have been stored for even up to 18 years in a biobank at -20°C.

Journal of Public Health

Aim To determine the risk of myocardial infarction (MI) associated with pattern, frequency, and i... more Aim To determine the risk of myocardial infarction (MI) associated with pattern, frequency, and intensity of alcohol consumption, type of alcoholic beverage, and the combined effect of alcohol and smoking on risk of MI, inflammation, and lipid profile. Method A total of 423 cases with a first MI and 465 controls from the Maltese Acute Myocardial Infarction (MAMI) Study were analysed. Data was collected through an extensive interviewer-led questionnaire, along with measurements of various blood parameters. Medians and the Mann–Whitney test were used to assess effect of different drinking patterns, frequency, intensity, and smoking and drinking combinations on hs-CRP and lipid profile. Odds ratios, adjusted for the conventional risk factors of MI (AdjORs), were calculated as an estimate of the relative risk of MI. Results Regular alcohol consumption protected against MI [AdjOR 0.6 (95% CI 0.4–0.9)] while daily binge drinking increased risk [AdjOR 5.0 (95% CI 1.6–15.0)] relative to reg...

Open Heart

Objective To investigate the effect of passive smoking, active smoking and smoking cessation on i... more Objective To investigate the effect of passive smoking, active smoking and smoking cessation on inflammation, lipid profile and the risk of myocardial infarction (MI). Methods A total of 423 cases with a first MI and 465 population controls from the Maltese Acute Myocardial Infarction (MAMI) Study were analysed. Data were collected through an interviewer-led questionnaire, and morning fasting blood samples were obtained. ORs adjusted for the conventional risk factors of MI (aORs) were calculated as an estimate of the relative risk of MI. The influence of smoking on biochemical parameters was determined among controls. Results Current smokers had a 2.7-fold (95% CI 1.7 to 4.2) and ex-smokers a 1.6-fold (95% CI 1.0 to 2.4) increased risk of MI. Risk increased with increasing pack-years and was accompanied by an increase in highsensitivity C reactive protein levels and an abnormal lipid profile. Smoking cessation was associated with lower triglyceride levels. Exposure to passive smoking increased the risk of MI (aOR 3.2 (95% CI 1.7 to 6.3)), with the OR being higher for individuals exposed to passive smoking in a home rather than in a public setting (aOR 2.0 (95% CI 0.7 to 5.6) vs aOR 1.2 (95% CI 0.7 to 2.0)). Passive smoke exposure was associated with higher levels of total cholesterol, triglycerides and total cholesterol:high-density lipoprotein cholesterol ratio compared with individuals not exposed to passive smoking. Conclusions Both active and passive smoking are strong risk factors for MI. This risk increased with increasing pack-years and decreased with smoking cessation. Such effects may be partly mediated through the influence of smoking on inflammation and lipid metabolism.

BMC Medical Genetics

Background: Mutations in Leucine-rich repeat kinase 2 NM_198578 (LRRK2 c.6055G > A (p.G2019S), LR... more Background: Mutations in Leucine-rich repeat kinase 2 NM_198578 (LRRK2 c.6055G > A (p.G2019S), LRRK2 c. 4321C > G (p.R1441G)) and alpha-synuclein NM_000345 (SNCA c.209G > A (p.A53T)) genes causing Parkinson's disease (PD) are common in Mediterranean populations. Variants in the Quinoid Dihydropteridine Reductase NM_000320 (QDPR c.68G > A (p.G23D)), Sepiapterin Reductase NM_003124 (SPR c.596-2A > G) and Methylenetetrahydrofolate Reductase NM_005957 (MTHFR c.677C > T and c.1298A > C) genes are frequent in Malta and potential candidates for PD. Methods: 178 cases and 402 control samples from Malta collected as part of the Geoparkinson project were genotyped for MTHFR polymorphisms, QDPR and SPR mutations. Only PD and parkinsonism cases were tested for SNCA and LRRK2 mutations. Results: LRRK2 c.4321C > G and SNCA c.209G > A were not detected. The LRRK2 c.6055G > A mutation was found in 3.1 % of Maltese PD cases. The QDPR mutation was found in both cases and controls and did not increase risk for PD. The SPR mutation was found in controls only. The odds ratios for MTHFR polymorphisms were not elevated. Conclusions: The LRRK2 c.6055G > A is a cause of PD in the Maltese, whilst QDPR c.68G > A, SPR c.596-2A > G and MTHFR c.677C > T and c.1298A > C are not important determinants of PD.