Familial Hypercholesterolaemia (FH) is an autosomal dominant disorder with a frequency of 1 in 250 to 500 in most European populations. It is characterised by a raised low density lipoprotein-cholesterol (LDL-C) and a high incidence of premature coronary heart disease (CHD). There are three genes where mutations are known to cause FH: the low-density lipoprotein receptor (LDLR) gene, the apolipoprotein B (APOB) gene and the pro-protein convertase subtilisin/kexin type 9 (PCSK9) gene. An FH-causing mutation can be found in around 40% of patients with a possible diagnosis of FH. It has been suggested that the patients with a clinical diagnosis of FH where no mutation were found might have a polygenic cause for their raised LDL-C. FH disorder is an under-diagnosed condition in many countries such as Poland. An analysis of a Polish FH cohort in this thesis, demonstrated the heterogeneous aetiology of FH. We found 39 different pathogenic mutations in the LDLR gene with 10 of them being novel and an overall detection rate of 43.4%. The aim of this thesis was to compare preclinical atherosclerosis between patients with monogenic FH and subjects with polygenic hypercholesterolaemia by means of a neck ultrasound to measure carotid Intima Media Thickness and a cardiac CT scan to assess coronary artery calcification. This study showed that preclinical atherosclerosis was greater in patients with monogenic FH. Lipoprotein(a) [Lp(a)] is a well-known biomarker for CHD risk prediction. The Lp(a) concentration and its association with two LPA single nucleotide polymorphisms (rs3798220 and rs6919346) were assessed in FH patients participating in the Simon Broome registry and a group of the general population participating in the Northwick Park Heart Study II. The results showed that the Lp(a) concentration and the frequency of rs3798220 was significantly higher in the FH patients compared to the general population.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:756266 |
| Date | January 2018 |
| Creators | Sharifi, Mahtab |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/10054674/ |
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