https://www.um.edu.mt/library/oar/handle/123456789/54170 2026-06-19T16:17:20Z https://www.um.edu.mt/library/oar/handle/123456789/65722 Title: The protein tyrosine phosphatase non-receptor type I (PTPN1) 1484InsG polymorphism in the Maltese population Abstract: The protein tyrosine phosphatase non-receptor type 1 gene (PTPNl) codes for the production of protein tyrosine phosphatase lB (PTPlB). This protein has been associated with the effective dephosphorylation of the insulin receptor resulting in the inhibition of insulin signaling. Its over expression has been associated with insulin resistance (Ahmad et al., 1997). The purpose of this study was to determine the allele frequency of the PTPNl 1484insG allele in the Maltese population and determine whether it is in Hardy-Weinberg equilibrium. A small study conducted by Zammit (2007) indicated the possibility that the PTPNl 1484insG polymorphism was not in Hardy Weinberg equilibrium in adult females subjects. For this reason newborns were used in the study. An allele frequency of 3.6% was observed in 196 Maltese newborns born in May/June 2011. This was considerably lower than that of the Italian population, which was 7.7% but it was similar to that observed in the Sicilian population which was 5.2% (Di Paola et al., 2002). There is an association between the PTPNl 1484insG polymorphism and high triglycerides, body mass index, total/HDL cholesterol and blood pressure (Di Paola et al., 2002). The involvement of the PTPNl 1484insG polymorphism in causing diabetes in the Maltese population still needs to be investigated. Description: B.SC.(HONS)APP.BIOMED.SCI. 2012-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/63468 Title: The effect of modifier genes on foetal Haemoglobin in the Maltese population Abstract: Haemoglobinopathies are a set of single-gene disorders that can be inherited throughout affected families. Such genetic diseases affect the correct formation and synthesis of the haemoglobin molecule. Various studies on patients with Hereditary Persistence of Foetal Haemoglobin (HPFH) have shown that three important genes, the cMYB proto-oncogene, the EKLF gene and the BCLJJA gene have a considerable impact in the regulation and control of foetal haemoglobin (HbF). Augmenting the level of HbF in sickle cell disease or β-thalassemia patients would greatly ameliorate the symptoms associated with these diseases. This can only be achieved by first understanding the genetic switch from foetal to adult haemoglobin that is commonly referred to as γ to β globin gene switching. In this study a combination of clinical research coupled with basic research was carried out. 22 β- thalassemia homozygotes and compound heterozygotes were recruited during the follow up clinical visits at the Thalassaemia and Molecular Genetics Clinic, Mater Dei Hospital, Malta. A complete blood count accompanied all blood samples to the laboratory. HbF and HbA2 measurements were conducted using a High-Pressure Liquid Chromatography. DNA genotyping of all samples was performed by TaqMan assays for HBSIL-MYB and BCLIJA polymorphisms. The results showed that even though HBSIL-MYB and BCLIIA are important HbF modifier genes, they do not explain the current HbF heterogeneity in the Maltese β thalassaemia patients. There was however a strikingly positive association between the BCL11A gene and reticulocyte count in Maltese female β thalassaemia patients that varied according to the mutant allele. Even though BCLIIA and HBSJL-MYB failed to reach a level of significance in this study, one must not completely omit further extension of the current work such as extending haplotypes in BCLJJA that surely warrant further investigation regarding their role in globin gene switching. Description: B.SC.(HONS)APP.BIOMED.SCI. 2012-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/63467 Title: Pharmacogenomic reactivation of foetal haemoglobin Abstract: Foetal haemoglobin (HbF) production in humans is controlled by many intricate mechanisms that to date remain partly understood. Pharmacogenomic studies aimed at understanding how particular compounds are able to induce HbF may help to elucidate the molecular control of globin switching. In this study, a collection of Maltese β-thalassaemia homozygotes and compound heterozygotes, healthy adults and KLF 1-haploinsufficient adults from Malta were explored. The effects of hydroxyurea (HU), thalidomide and 5-Aza-2'-deoxycytidine, all wellknown HbF inducing agents, were studied in an effort to identify whether they augment HbF and to what extent. Of all the groups tested, the fold change increase of HbF was not always easy to interpret since the β-thalassaemia homozygotes and compound heterozygous patients and the KLF 1 haploinsufficient patient had a higher HbF to start off with as a baseline and hence fold change increase tended to be somewhat lower than in the healthy adults. The data presented here underline for the first time a role for KLF 1 inhibition by drugs in culture (in vitro) in human haematopoiesis and suggest that the KLF 1 gene may be an important pharmacogenomic marker to predict efficacy to HU, thalidomide or 5-Aza-2'-deoxycytidine treatment. Comparisons conducted between different HbF expression profiles across the three groups, that included low and high HbF scenarios and "responders" versus "non-responders" for HU, thalidomide and 5Aza-2' -deoxycytidine treatment, the augmentation of HbF may be partially explained by down regulation of KLF 1. Drugs in culture have inhibited this gene, and more or less provided similar evidence to the results obtained across multiple testing scenarios and different groups. The effect on HbF by the drugs in culture was evident at 24 hrs in the healthy adults whilst more pronounced at 72 hrs for the β-thalassaemia homozygotes and compound heterozygous patients and the KLF1 haploinsufficient patient. Description: B.SC.(HONS)APP.BIOMED.SCI. 2012-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/63466 Title: Evaluating faecal tumour M2 Pyruvate Kinase as a screening test for colorectal carcinoma Abstract: Colorectal carcinoma (CRC) is the third most common malignancy worldwide. Screening for CRC is linked with a decreased incidence of the disease and also a lowered mortality rate. Most screening programs have relied on Guaiac-based Faecal Occult Blood Test (G-FOBT); however this test has the main limitation of being poorly sensitive to CRC since it fails to detect non-bleeding colorectal adenomas and CRC. Tumour M2 Pyruvate Kinase (Tumour M2-PK) is the dimeric form of pyruvate kinase and is characteristically found in proliferating cells, especially tumour cells. In CRC and to a lesser extent in colorectal adenomas, Tumour M2-PK is released into the stools and may be quantified using an Enzyme-linked immunosorbent assay (ELISA). The aim of this study was to compare Faecal Tumour M2-PK assay and G FOBT head-to-head using colonoscopy as the gold standard. Faecal Tumour M2-PK assay and G-FOBT were evaluated in 30 patients undergoing colonoscopy of which 22 patients were normal or had hyperplastic/inflammatory polyps only, 5 patients had low-grade dysplasia colorectal adenomas while 3 patients had other gastro-intestinal tract (GIT) inflammatory conditions. Specificity and sensitivity of G-FOBT for colorectal adenomas were 100% and 0% respectively while specificity and sensitivity of faecal Tumour M2-PK for colorectal adenomas were 84 - 95.5% (depending if results of patients with GIT inflammatory conditions are included) and 20% respectively. This study showed that both tests have no potential in discriminating between normal individuals and patients bearing adenomas; therefore these tests may have very limited role in decreasing CRC incidence rate and should not be recommended as screening tests for CRC. Description: B.SC.(HONS)APP.BIOMED.SCI. 2012-01-01T00:00:00Z