Uloga polimorfizama kandidatskih gena za kardiovaskularne bolesti u dugovječnosti: antropološki pristup

doctoral thesis

• Title (english): The role of polymorphisms in candidate genes for cardiovascular diseases in longevity: anthropological approach
• Author: Matea Zajc Petranović
• Mentor: Tatjana Škarić-Jurić (mentor)
• Committee member: Krunoslav Brčić-Kostić (član povjerenstva)
• Committee member: Ana Galov (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2013, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 575 - General genetics. General cytogenetics

Abstract

Kardiovaskularne su bolesti (KVB) glavni uzročnik pobola i smrtnosti diljem svijeta, a podložnost razvoju bolesti povećava interakcija okolišnih, biokemijskih i genetičkih čimbenika rizika. Kako dugovječnost nije ništa drugo nego izbjegavanje smrtnog ishoda, provedena je analiza povezanosti četiriju polimorfizama kandidatskih gena za KVB (ACE, APOE, eNOS, MTHFR) s negenetičkim čimbenicima rizika u uzorku osoba starijih od 80 godina. Logistička regresija je pokazala da kombinacija genotipova ACE-DD i MTHFR-CC smanjuje šansu doživljenja duboke starosti (≥90 g.) prema modelu koji objašnjava čak 27,5% varijance. Meta-analiza učestalosti javljanja ispitivanih alela kod opće populacije u odnosu na osobe starije od 80 godina, koja je provedena korištenjem literaturnih podataka za Europske populacije, je pokazala da su D alel ACE gena i E2 alel APOE gena češći su kod osoba starih 80+ godina, dok je E4 alel češći kod opće populacije. Istraživanje je ukazalo na prisutnost selektivnog mortaliteta kod nosioca E4 alela APOE gena kao i na zavisne od dobi, pleiotropne učinke ACE I/D polimorfizma.

Abstract (english)

Cardiovascular diseases (CVDs) are the major cause of morbidity and mortality worldwide, and the susceptibility to developing CVD is increased by the interaction of several environmental, biochemical and genetic risk factors. Since longevity is nothing but avoiding death, the association analysis of polymorphisms in four candidate genes for CVDs (ACE, APOE, eNOS, MTHFR) with non-genetic risk factors was performed in a sample od people aged 80 years and over. Logistic regression analysis showed that the combination of ACE-DD and MTHFR-CC genotypes reduced the chance of survival into nonagenarian age, in a model explaining as much as 27.5% of the variance. The meta-analysis, carried out using published data for the European populations, tested the frequency of the investigated alleles between general and 80+ population, and showed that ACE D allele and APOE E2 allele were more common in elderlies, while E4 allele was more common in general population. This research indicated the existence of selective mortality in APOE E4-carriers, as well as the age- dependent, pleiotropic effects of the ACE I/D polymorphism.

• Keywords: dugovječnost; kandidatski geni; polimorfizmi; kardiovaskularne bolesti; populacija 80+; meta-analiza
• Keywords (english): longevity; candidate genes; polymorphisms; cardiovascular diseases; population 80+; meta-analysis
• Language: croatian
• URN:NBN: urn:nbn:hr:217:413621
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-05-22 07:38:35