Uloga polimorfizama gena CYP2J2 u kliničkoj medicini

master's thesis

• Title (english): The role of CYP2J2 gene polymorphisms in clinical medicine
• Author: Magdalena Jurič
• Mentor: Dunja Rogić (mentor)
• Mentor: LIVIJA ŠIMIČEVIĆ (mentor)
• Committee member: Dunja Rogić (predsjednik povjerenstva)
• Committee member: LIVIJA ŠIMIČEVIĆ (član povjerenstva)
• Committee member: Anita Somborac Bačura (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2023-07-06, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry

Abstract

Enzimi citokrom P450 (CYP) imaju ključnu ulogu u stvaranju epoksieikozatrienoičnih kiselina (EET), metabolita
arahidonske kiseline koji ostvaruju različite zaštitne i protuupalne učinke, prvenstveno na kardiovaskularni sustav. One potiču
vaskularnu relaksaciju, angiogenezu i fibrinolizu, djeluju protuupalno te moduliraju aktivnost ionskih kanala. CYP2J2 je glavni
enzim odgovoran za epoksidaciju arahidonske kiseline u EET u srcu i koronarnim arterijama. Polimorfizam CYP2J2 *7 u
promotorskoj regiji gena smanjuje njegovu ekspresiju za 48 % što rezultira smanjenom koncentracijom EET, disregulacijom
proupalnih i profibrotičkih čimbenika te promijenjenom aktivnosti ionskih kanala. Kako su upravo ti mehanizmi uključeni u
nastanak fibrilacije atrija, hipoteza ove studije jest kako postoji povezanost polimorfizma CYP2J2 *7 i fibrilacije atrija. Budući
da CYP2J2 nije eksprimiran u venama te ne doprinosi patogenezi venske tromboze, genotipizirano je 179 ispitanika s
fibrilacijom atrija te 102 ispitanika s trombozom. Učestalost alela CYP2J2 *7 u ispitivanoj populaciji bila je 5,51 %. Zbog istih
čimbenika rizika za obje bolesti, nije bilo značajne razlike u učestalosti dislipidemije, hipertenzije i šećerne bolesti, ali su se
ispitanici razlikovali s obzirom na dob i spol. Regresijsko analizom utvrđeno je kako prisutnost barem jednog varijantnog alela
*7 povećava omjer vjerojatnosti za razvoj fibrilacije atrija. Analizirajući podatke prema spolu, nije utvrđena razlika u
učestalosti genotipova kod muškaraca dok je kod žena razlika bila statistički značajna (p = 0,047). Pripadajući omjer
vjerojatnosti za razvoj fibrilacije atrija kod žena iznosio je 4,010 (95 % CI: 1,127 – 19,041). Sveukupno, rezultati ovog
istraživanja upućuju kako polimorfizam CYP2J2 *7 može pridonijeti povećanom riziku za razvoj fibrilacije atrija u hrvatskoj
populaciji, osobito u žena.

Abstract (english)

Cytochrome P450 (CYP) enzymes play a crucial role in the formation of epoxyeicosatrienoic acids (EETs),
metabolites of arachidonic acid which have various protective and anti-inflammatory effects, particularly on the cardiovascular
system. CYP2J2 is the key enzyme responsible for epoxidation of arachidonic acid into EETs in the heart and coronary arteries.
The presence of the CYP2J2 *7 polymorphism in the gene's promoter region reduces its expression by 48% which,
consequently, leads to decreased EET concentrations, dysregulation of proinflammatory and profibrotic factors, and altered ion
channel activity. As these mechanisms are involved in the development of atrial fibrillation, the hypothesis of this study is that
there is an association between CYP2J2 *7 polymorphism and atrial fibrillation. Since CYP2J2 is not expressed in veins and
has no significant contribution to the pathogenesis of venous thrombosis, 179 subjects with atrial fibrillation and 102 subjects
with thrombosis were genotyped. In the studied population the frequency of the CYP2J2 *7 allele was 5.51%. Due to similar
risk factors for both diseases, no significant differences between groups were observed in the frequency of dyslipidemia,
hypertension, and diabetes. However, differences in age and gender were found. Regression analysis revealed that the
occurrence of at least one variant allele *7 increased the odds ratio of atrial fibrillation. The difference in genotype frequency
was not determined in men, but a statistically significant difference (p = 0.047) was observed in women. The corresponding
odds ratio of atrial fibrillation for women was 4.010 (95 % CI: 1.127 – 19.041). Overall, the results imply that the CYP2J2 *7
polymorphism may contribute to an increased risk of atrial fibrillation in the Croatian population, especially in women.

• Keywords: bioaktivni lipidni medijatori; CYP2J2; epoksigenaza; kardiovaskularne bolesti; polimorfizmi gena; višestruko nezasićene masne kiseline
• Keywords (english): bioactive lipid mediators; cardiovascular diseases; CYP2J2; epoxygenase; gene polymorphisms; polyunsaturated fatty acids
• Language: croatian
• URN:NBN: urn:nbn:hr:163:139400
• Study programme: Title: Medical biochemistry; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra medicinske biokemije (magistar/magistra medicinske biokemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-11-21 14:48:08