Povezanost polimorfizama gena estrogenskoga receptora alfa i interleukina 6 s endotelnom funkcijom u asimptomatskih potomaka bolesnika s ranom koronarnom bolesti i akutnim koronarnim sindromom

doctoral thesis

• Title (english): Correlation of estrogen receptor alfa gene and interleukin 6 polymorphism with entothelial function in asymptomatic descendants of patients with early coronary disease and acute coronary syndrome
• Author: Zoran Miovski
• Mentor: Ljiljana Banfić (mentor)
• Committee member: Diana Delić-Brkljačić (predsjednik povjerenstva)
• Committee member: Jadranka Sertić (član povjerenstva)
• Committee member: Nikola Bulj (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2023-03-08, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Estrogeni štite od endotelne disfunkcije te djeluju na metabolizam lipida, a određeni su polimorfizmi u genu ERα u ranijim studijama povezivani s koronarnom bolešću. IL-6 pak ima centralnu ulogu u procesu upale, te je polimorfizam gena za IL-6 kao i plazmatske koncentracije IL-6 i CRP-a ranije povezivan s ACS-om. Funkcija endotela se može procijeniti neinvazivno i na perifernim arterijama, pomoću ultrazvučnog testa FMD. Cilj ovog istraživanja bio je analizirati povezanost polimorfizma gena ERα (duljina T/A ponavljanja) i polimorfizma gena IL-6 (174G>C) u potomaka bolesnika s ranom koronarnom bolešću s endotelnom disfunkcijom korištenjem FMD metode. Pritom je analizirana i prevalencija ovih polimorfizama u obje populacije, povezanost polimorfizma gena ERα i patoloških vrijednosti lipidograma, kao i povezanost polimorfizma gena IL-6 i patoloških vrijednosti plazmatskog CRP-a. Rezultati ovog rada su pokazali visoku pojavnost heterozigotne i homozigotne „duge“ alelne forme polimorfizma ERα u bolesnika s ranom koronarnom bolesti - u čak 76% njih te visoku pojavnost heterozigotne i homozigotne alelne forme polimorfizma IL-6, prisutne u 56% bolesnika. Pritom je prvi puta istražena učestalost ovih polimorfizama u djece potomaka ranih koronarnih bolesnika, koja je nađena u 78% za polimorfizam ERα i 66% za polimorfizam IL-6. Također, „kratka“ alelna forma polimorfizma ERα („divlji“ tip) u ovom radu imala je utjecaj na vrijednosti plazmatskih lipida u muških bolesnika i muških potomaka koji su imali statistički značajno više vrijednosti LDL-a. Isto tako, prisustvo homozigotne i heterozigotne alelne forme polimorfizma IL-6 bilo je povezano s povišenim vrijednostima CRP-a u 32% bolesnika s ranom koronarnom bolešću naspram njih 18% s „divljim“ tipom. Potomci bolesnika s ranom koronarnom bolešću s nasljeđene obje homozigotne forme polimorfizma ERα i IL-6 su imali najniže izmjerene vrijednosti FMD-a s dvostruko nižim medijanom od potomaka s „divljim“ tipom oba polimorfizma. Zaključno, ova studija govori u prilog moguće uloge polimorfizma gena ERα i IL-6 u endotelnoj disfunkciji prema pokazateljima dobivenim FMD metodom, no potrebna su dodatna istraživanja kako bi se procijenila njihova potencijalna upotreba kao biomarkera rane koronarne bolesti.

Abstract (english)

Estrogens protect from endothelial dysfunction as well as affect lipid metabolism and certain polymorphisms in the ERα gene have been associated with coronary disease in earlier studies. IL-6 plays a central role in the inflammation process, and polymorphism of the IL-6 gene as well as plasma concentrations of IL-6 and CRP, were also associated with ACS in previous studies. Endothelial function can be assessed non-invasively on peripheral arteries, using the FMD test. The aim of this research was to analyze the association of ERα gene polymorphism (T/A repeat length) and IL-6 gene polymorphism (174G>C) in the offspring of patients with early coronary disease and endothelial dysfunction using the FMD method. This study analyzed the prevalence of these polymorphisms in both populations, as well as the association of ERα gene polymorphism with pathological lipidogram values, as well as the association of IL-6 gene polymorphism with pathological plasma CRP values. Study showed a high incidence of heterozygous and homozygous "long" allelic forms of the ERα polymorphism in patients with early coronary disease - in as many as 76% of them, and a high incidence of heterozygous and homozygous allelic forms of the IL-6 polymorphism, present in 56% of patients. This study is the first to investigate the frequency of these polymorphisms in the children early coronary patients, and found them in 78% for the ERα polymorphism and 66% for the IL-6 polymorphism. Also, the "short" allelic form of the ERα polymorphism ("wild" type) in our study had an impact on plasma lipid values in male patients and male offsprings, who had significantly higher LDL values. Likewise, the presence of homozygous and heterozygous allelic forms of the IL-6 polymorphism was associated with increased CRP values in 32% of patients with early coronary disease compared to 18% with the "wild" type. The offspring of patients with early coronary disease who inherited both homozygous forms of the ERα and IL-6 polymorphisms had the lowest measured FMD values with a median twice as low as the offspring with the "wild" type of both polymorphisms. In conclusion, this study supports the possible role of ERα and IL-6 polymorphism in the endothelial dysfunction detected with FMD, but additional studies are needed in order to investigate their potential use as a biomarker of early coronary disease.

• Keywords: Metabolizam lipida; Estrogeni; Polimorfizam; genetski; Koronarna bolest; Biomarkeri; Upala; Lipidi
• Keywords (english): Lipid Metabolism; Estrogens; Polymorphism; Genetic; Coronary Artery Disease; Biomarkers; Inflammation; Lipids
• Language: croatian
• URN:NBN: urn:nbn:hr:105:350617
• 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: 109 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-03-28 11:45:07