Hiperkolesterolemia Familiarra: PCSK9 aldaeren karakterizazioa tratamendu pertsonalizaturako

Abstract

Gaixotasun kardiobaskularrak mundu mailan heriotza gehien sortzen dituzten arrazoiak dira, gehienbat bizimodu ez osasuntsuagatik. Hala ere, badaude banako batzuk zeintzuek arrazoi genetikoen erruz pairatzen dituzten, Hiperkolesterolemia Familiarra (HF) izeneko gaixotasun autosomiko gainartzaile bat izanik. 3 geneetan gertatzen dira aldaerak batez ere: LDLR, ApoB eta PCSK9. Aldaeren identifikazioa, mekanismoa ezartzea eta tratamendua sortzea oso zaila da, baina beharrezkoa gaixotasunaren aurka egiteko. Ikerketa honen helburua funtzio-irabaztea duten 7 PCSK9 aldaeren karakterizazio funtzionala era ziur eta erraz batean egitea ahalbidetzen duen metodologia bat sortzea izan da, tratamendu pertsonalizatua emateko. Horretarako, PCSK9-ren polimorfismo ohikoenak karakterizatu dira sakonki.

Cardiovascular diseases are the main worldwide reason of death, especially due to non-healthy lifestyle. However, there are some individuals that suffer from it due to genetic reasons, having an autosomic dominant disease called Familiar Hypercholesterolemia (FH). Mutations occur mostly in 3 genes: LDLR, ApoB and PCSK9. The identification, the stablishing of the mechanism and developing of treatment are very difficult processes, but they are necessary to face up the disease. The goal of this research is to set up an easy and reliable methodology to functionally characterize the activity of PCSK9 gain of function variants in order to provide a personalized treatment. Therefore, we have extensively characterized the seven more common gain-of-function PCSK9 variants.