Populacijsko-genetičke i okolišne odrednice metaboličkog sindroma u populaciji otoka Visa

doctoral thesis

• Title (english): Population-genetics and environmental determinants of metabolic syndrome in the population of island Vis
• Author: Ivana Kolčić; MBZ: 271736
• Mentor: Ariana Vorko Jović (mentor)
• Committee member: nije dostupno (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2009-02-23, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Public Health and Health Care
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

Cilj ovog istraživanja bio je istražiti populacijsko-genetičke i okolišne odrednice metaboličkog sindroma u odrasloj populaciji otoka Visa. U tu svrhu provedeno je terensko prikupljanje podataka tijekom 2003. i 2004. godine i u istraživanje je uključeno 1.024 ispitanika. Za svakog ispitanika proveden je niz fenotipskih mjerenja, prikupljeni su podaci o rodbinskim vezama i provedena je genotipizacija korištenjem mikrosatelitnih biljega i polimorfizama jednog nukleotida (SNP). Prevalencija metaboličkog sindroma iznosila je 48% prema ATP III definiciji (38% za muškarce, 56% za žene) i 58% prema IDF definiciji (46% za muškarce, 66% za žene). Dobno standardizirana prevalencija prema ATP III definiciji bila je 33% (26% za muškarce, 40% za žene), a prema IDF definiciji iznosila je 42% (33% za muškarce, 50% za žene). Ukupno je 86% ispitanika jednako klasificirano prema obje definicije. Nakon rezultata bivarijatnih analiza u kojima je pronađena statistički značajna povezanost metaboličkog sindroma s nizom čimbenika, u mješovitom regresijskom modelu zadržala se statistički značajna povezanost za dob, spol, HOMA indeks inzulinske rezistencije te koncentracije inzulina, tPA, mokraćne kiseline, fibrinogena i kortizola. Povećanje osobne heterozigotnosti genoma bila je obrnuto proporcionalno povezana sa šansom za dijagnozu metaboličkog sindroma. Heritabilnost metaboličkog sindroma bila je 34% za ATP III definiciju i 43% za IDF definiciju, ali su okolišni čimbenici objasnili veći postotak varijance metaboličkog sindroma; 51% prema ATP III definiciji i 56% prema IDF definiciji. U cjelogenomskoj analizi pronađena su četiri SNP biljega koji su bili statistički granično neznačajno povezani s metaboličkim sindromom, od kojih je u modelu logističke regresije statistički značajna povezanost potvrđena za dva biljega (rs3881953 koji je ujedno bio povezan s opsegom struka i rs10511595 koji je bio povezan sa serumskom koncentracijom glukoze). Rezultati ovog istraživanja na izoliranoj populaciji otoka Visa govore u prilog većoj važnosti okolišnih čimbenika kao odrednica metaboličkog sindroma u odnosu na genetičke čimbenike, uz istovremeno razmjerno visoke vrijednosti heritabilnosti. Zbog visoke prevalencije metaboličkog sindroma u populaciji otoka Visa, potrebno je osmisliti i provesti javno-zdravstvenu intervenciju s ciljem smanjivanja prevalencije metaboličkog sindroma koji je jedan od značajnijih kardiovaskularnih čimbenika rizika.

Abstract (english)

The aim of this study was to investigate the genetic and environmental determinants of metabolic syndrome among the adult inhabitants of island Vis. A total of 1,024 respondents were recruited during 2003 and 2004. A number of phenotypic measurements were made for each respondent, supplemented with the genealogical information and genotypes (microsatellites and single nucleotide polymorphisms, SNP). The prevalence of metabolic syndrome was 48% using ATP III definition (38% for men and 56% for women), and 58% using IDF definition (46% for men and 66% for women). Age-standardised prevalence using ATP III was 33% (26% for men and 40% for women), while IDF definition yielded the age-standardised prevalence of 42% (33% for men and 50% for women). Definitions overlaped in 86% of all cases. While bivariate analysis revealed numerous associations, mixed model results yielded significant association of metabolic syndrome with age, gender, HOMA index, insulin, tPA, uric acid, fibrinogen and cortisol. Individual genome-wide heterozygosity was inversely associated with the metabolic syndrome odds. Metabolic syndrome heritability was 34% when ATP III definition was used, and 43% for IDF definition, but environmental contribution to the metabolic syndrome variance was higher; percent of explained variance was 51% for ATP III and 56% for IDF definition. Genome-wide analysis implied four SNPs, two of which were significantly associated with metabolic syndrome in the logistic regression model (rs3881953 was also associated with waist circumference, and rs10511595 was associated with serum glucose level). Overall results indicate higher environmental variance share, nevertheless with high heritability. High prevalence of metabolic syndrome in the adult population of island Vis requires public health intervention, aiming to reduce the prevalence of metabolic syndrome as one of the most important cardiovascular disease risk factors.

• Keywords: medicina
• Keywords (english): medicine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:533536
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
• Type of resource: Text
• Extent: 201 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-05-05 08:52:12