Polimorfizmi gena RAD50, STARD3, ORMDL3 i IL6R u bolesnika s astmom

doctoral thesis

• Title (english): Gene RAD50, STARD3, ORMDL3 and IL6R polymorphisms in asthmatic patients
• Author: Anamarija Štajduhar
• Mentor: Sanja Popović-Grle (mentor)
• Committee member: Marko Jakopović (predsjednik povjerenstva)
• Committee member: Mirjana Turkalj (član povjerenstva)
• Committee member: Marija Gomerčić Palčić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2024-12-10, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Unatoč značajnom medicinskom napretku u posljednjih nekoliko desetljeća, astma se još uvijek smatra izazovom. Ovo je prva slučaj-kontrola studija gena kandidata u Hrvatskoj kojoj je cilj razjasniti genomski kontekst pojave astme u odraslih. Hipoteza istraživanja je bila da su polimorfizmi gena IL6R (1q21.3), RAD50 (5q31.1), STARD3 i ORMDL3 (17q12-21.1) povezani s ranijom pojavom bolesti, težom astmom, većim brojem egzacerbacija te alergijskim oblikom astme. U istraživanju je sudjelovalo 235 ispitanika s astmom težine 1-4 (od blage do teške astme) po GINA kriterijima. Našlo se da su polimorfizmi RS2897443 i RS2244012 (RAD50) rizični čimbenik za razvoj nosne polipoze, RS1877031 (STARD3) rizični je čimbenik za pojavu astme u djece i razvoj nosne polipoze, ali djeluje zaštitno na prisutnost astme i pojavu bolesti u odraslih te nastanak T2 alergijskog i eozinofilnog fenotipa. RS3744246 gena ORMDL3 nosi povećan rizik za prisutnost astme u odraslih iako je uz njega ona bolje kontrolirana dok su za SNP gena IL6R, RS4129267, nađene samo asocijacije na razini pojedinih genotipova za prisutnost astme u odraslih i visoke vrijednosti krvne eozinofilije i FeNO-a. Zaključno, astma je kompleksna bolest i ovdje se dokazalo da spoznaje o genetskoj podlozi patofizioloških procesa dobivenih iz dječjih populacija nisu nužno i odraz situacije u populaciji odraslih.

Abstract (english)

Despite significant medical advances in recent decades, asthma is still considered a challenge. This is the first candidate genes case-control study in Croatia that aims to clarify the genomic context of asthma in adults. The research hypothesis was that IL6R (1q21.3), RAD50 (5q31.1), STARD3 and ORMDL3 (17q12-21.1) gene polymorphisms were associated with an earlier disease onset, more severe asthma, a greater number of exacerbations and an allergic asthma phenotype. A total of 235 subjects with asthma, stage 1-4 (from mild to severe asthma) according to GINA criteria, took part in this research. It was found that the polymorphisms RS2897443 and RS2244012 (RAD50) are a risk factor for the development of nasal polyposis, RS1877031 (STARD3) is a risk factor for the onset of asthma and the development of nasal polyposis in children, but has a protective effect on the presence of asthma and the onset of the disease in adults and the occurrence of T2 allergic and eosinophilic phenotype. RS3744246 of the ORMDL3 gene carries an increased risk for the presence of asthma in adults, although it conffers a better controlled variant, while for the SNP of the IL6R gene, RS4129267, the only associations were found at the level of individual genotypes for the presence of asthma in adults and high values of blood eosinophilia and FeNO. In conclusion, asthma is a complex disease and here it has been proven that the knowledge about the genetic basis of pathophysiological processes in asthma obtained

• Keywords: astma; fenotip; polimorfizmi jednog gena; IL6R; RAD50; STARD3; ORMDL3
• Keywords (english): asthma; phenotype; single gene polymorphisms; IL6R; RAD50; STARD3; ORMDL3
• Language: croatian
• URN:NBN: urn:nbn:hr:105:238532
• 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: 96 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-12-19 08:11:31