Povezanost polimorfizma ACE-gena s težinom kliničke slike bolesnika sa sistemskom sklerozom

doctoral thesis

• Title (english): Association between ACE gene polymorphism and severity of clinical presentation in patients with systemic sclerosis
• Author: Boris Karanović
• Mentor: Branimir Anić (mentor)
• Committee member: Joško Mitrović (predsjednik povjerenstva)
• Committee member: Hrvoje Lalić (član povjerenstva)
• Committee member: Miroslav Mayer (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Physiology and Immunology); Zagreb
• Defense date and country: 2024-12-02, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Clinical Immunology
• Universal decimal classification (UDC): 612 - Physiology

Abstract

Uvod: Sistemsku sklerozu (SSc) obilježava autoimunost, upala, vaskulopatija i fibroza. U sličnim patofiziološkim mehanizmima sudjeluje sustav renin-angiotenzin (RAS) čija je središnja molekula enzim za pretvorbu angiotenzina (ACE). Njegova aktivnost ovisi o insercijskom (II), delecijskom (DD) i kodominantnom (ID) polimorfizmu u intronu 16 ACE-gena, pri čemu nosioci polimorfizma DD naspram II imaju dvostruko veću aktivnost ACE.

Hipoteza: Bolesnici s polimorfizmom DD ACE-genotipa imaju težu kliničku sliku SSc.

Cilj: Ispitati povezanost ACE-genotipa s fenotipskim obilježjima oboljelih od SSc.

Ispitanici i metode: Provedena je retrospektivna analiza povezanosti polimorfizma ACE-gena s težinom manifestacija SSc na više organskih sustava pri postavljanju dijagnoze u 135 bolesnika, nakon 5 godina u 105 i nakon 10 godina praćenja u 70 bolesnika.

Rezultati: Nije nađena statistički značajna povezanost polimorfizma ACE-gena s težinom kliničke slike SSc. Međutim, u vremenskoj točki nakon deset godina zabilježena je statistički značajna razlika između 3 genotipa u vrijednosti komponente komplementa C4 (najniža vrijednost u genotipu II, a najviša u genotipu DD) te istisne frakcije lijeve klijetke (LVEF; najniža vrijednost u genotipu ID, a najviša u DD). Tijekom desetogodišnjeg perioda došlo je do statistički značajnog pada vrijednosti sedimentacije eritrocita (SE) i forsiranog ekspiracijskog volumena tijekom prve sekunde (FEV1) u genotipu ID te do značajnog povećanja ukupnog zbroja bodova na Medsgerovoj ljestvici težine bolesti u genotipu II i ID.

Zaključak: Hipoteza da bolesnici s polimorfizmom DD ACE-gena imaju težu kliničku sliku SSc nije potvrđena. Međutim, genotipovi II i ID mogli bi biti prediktori progresije bolesti.

Abstract (english)

Introduction: Systemic sclerosis (SSc) is characterized by autoimmunity, inflammation, vasculopathy and fibrosis. Renin-angiotensin system (RAS) is implicated in similar pathophysiological mechanisms. The central molecule of RAS is angiotensin converting enzyme (ACE) whose activity is regulated by the insertion (II), deletion (DD) or codominant (ID) polymorphism in introne 16 of the ACE gene. DD polymorphism carriers have twice the ACE activity of those with II polymorphism.

Hypothesis: ACE DD polymorphism carriers have more severe multiorgan manifestations of SSc.

Aim: Analysis of the association between ACE gene polymorphism and phenotypic features of SSc.

Patients and methods: Analysis of the association between severity of SSc multiorgan manifestations and ACE gene polymorphism was performed in 135, 105 and 70 patients at the time of diagnosis, after 5 and 10 years of follow-up, respectively.

Results: No statistically significant association between ACE gene polymorphism and the severity of multiorgan SSc manifestations was found. At a time point after 10 years of follow-up, statistically significant differences between the 3 genotypes were found in C4 complement levels (lowest values in II, highest in DD genotype) and left ventricular ejection fraction (LVEF; lowest values in ID, highest in DD genotype). During 10 years of follow-up, there was a statistically significant decrease in erythrocyte sedimentation rate (ESR) and forced expiratory volume during the first second (FEV1) in genotype ID and increase in total sum of Medsger severity index in genotypes II and ID.

Conclusion: Hypothesis that ACE DD polymorphism carriers have more severe multiorgan SSc manifestations has been rejected. II and ID genotype could be biomarkers of disease progression.

• Keywords: Peptidil-dipeptidaza A; Renin-angiotenzinski sustav; Autoimunost; Polimorfizam; genetski; Sklerodermija; sistemska; Fibroza; Biomarkeri
• Keywords (english): Peptidyl-Dipeptidase A; Renin-Angiotensin System; Autoimmunity; Polymorphism; Genetic; Scleroderma; Systemic; Fibrosis; Biomarkers
• Language: croatian
• URN:NBN: urn:nbn:hr:105:177231
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 134 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-12-06 11:55:04