Povezanost polimorfizama gena za serotoninski transportni sustav s fenotipom Crohnove bolesti

doctoral thesis

• Title (english): Rad ne sadrži naslov na drugom jeziku.
• Author: Katja Grubelić Ravić; VIAF: 305796082
• Mentor: Boris Vucelić (mentor)
• Committee member: Neven Ljubičić (predsjednik povjerenstva)
• Committee member: Marko Banić (član povjerenstva)
• Committee member: Nada Božina (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2020-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

U ovoj retrospektivnoj case-control studiji izvršena je analiza povezanosti alelnih i genotipskih formi promotorske (5-HTTLPR i rs25531) i Stin2 VNTR polimorfne regije SLC6A4 gena sa pojavnošću Crohnove bolesti (CD). Istraživanjem je obuhvaćeno 192 CD pacijenata i 157 zdravih kontrolnih (HC) ispitanika (po dobi i spolu ujednačenih sa skupinom pacijenata). Genotipizacija ispitanika izvršena je lančanom reakcijom polimeraze a korelacija polimorfnih varijanti SLC6A4 gena sa kliničkim i fenotipskim karakteristikama ispitanika analizirana je primjenom χ2 odnosno Fisherovog egzaktnog testa, univarijantnom i multivarijantnom logističkom regresijom te analizom haplotipova. Rezultati su potvrdili podjednaku spolnu (CD: 88 (45.8%) žene, 104 (54.2%) muškarci; HC: 84 (53.5%) žene, 73 (46.5%) muškarci; χ2 = 2.03, df =1, P = 0.154) i starosnu (CD: 41.34±12.789; HC: 41.68±8.789; P = 0.091) distribuciju unutar CD i HC skupine ispitanika. Statistički značajna razlika u distribuciji alela i genotipova između CD i HC te između ženske podskupine pacijenata u odnosu na odgovarajuću kontrolnu skupinu ispitanika utvrđena je za STin2 VNTR polimorfnu regiju SLC6A4 gena [distribucija genotipova (CD χ2 = 12.03; df = 2, P = 0.002; žene: χ2 = 9.85, df = 2; P = 0.007 ); distribucija alela (CD: χ2 = 12.03; df = 2, P = 0.002; žene: χ2 = 9.85, df = 2; P = 0.007)]. Utvrđena je statistički značajna negativna povezanost bialelne ss (s = STin2 10 ili STin2 9) genotipske forme STin2 VNTR lokusa [CD: P = 0.013, OR (prilagođeno po dobi i spolu) = 0.5, 95% CI=0.29-0.86; žene: P = 0.006, OR (prilagođeno po dobi )= 0.32, 95% CI=0.14-0.72] sa pojavnošću CD-a te statistički značajno veća zastupljenost S-STin2.12 (5-HTTLPR/rs25531: S-STin2: STin2.12) haplotipa u CD skupini ispitanika (P = 0.004, OR=1.62, 95 % CI=1.16-2.26). Nije utvrđena statistički značajna povezanost alelnih i genotipskih formi 5-HTTLPR i rs25531 SNP polimorfne regije SLC6A4 gena sa CD-om kao ni razlika u njihovoj distribuciji između različitih fenotipskih formi Crohnove bolesti klasificiranih prema Montrealskom konsenzusu. Zaključno, prikazani rezultati ukazuju na potencijalno važan doprinos STin2 VNTR polimorfne regije SLC6A4 gena u patogenezi Crohnove bolesti.

Abstract (english)

In this retrospective case-control study we analyzed the potential association of the promoter (5-HTTLPR and rs25531) and intronic Stin2 VNTR polymorphic regions of the SLC6A4 gene with the incidence of Crohn's disease (CD). The study included 192 CD patients and 157 healthy control subjects (age and gender matched with patients group). Genotyping was performed by polymerase chain reaction and correlation of polymorphic SLC6A4 gene variants with CD and its clinical subtypes was analyzed by chi-square and Fisher's exact test, binary logistic regression and haplotype analysis. The results confirmed similar gender (CD: 88 (45.8%) female, 104 (54.2%) male; HC: 84 (53.5%) female, 73 (46.5%) male; χ2 = 2.03, df =1, P = 0.154) and age (CD: 41.34±12.789; HC: 41.68±8.789; P = 0.091) distribution among CD and HC groups involved in the study. Significant difference was observed in STin2 genotype (CD: χ2=15.86, df = 4, P = 0,003; females: χ2 = 15.33, df = 4, P = 0.004) and allele (CD: χ2 = 12.03; df = 2, P = 0.002; females: χ2 = 9.85, df = 2; P = 0.007) distribution between CD and HC and between corresponding female subgroups, with significant negative association (CD: P = 0.013, OR adjusted by age and gender = 0.5, 95% CI=0.29-0.86; females: P = 0.006, OR adjusted by age = 0.32, 95% CI=0.14-0.72) of biallelic ss (STin2.9 and Stin2.10) STin2 genotype with CD, and significantly higher S-STin2.12 ( 5-HTTLPR/rs25531: S-STin2: STin2.12) haplotype distribution (P = 0.004, OR=1.62, 95 % CI=1.16-2.26) in CD. There was no significant association between 5-HTTLPR and rs25531 genotype or allele frequencies and CD or between any SLC6A4 polymorphic loci among different clinical subtypes of Crohns disease classified according to Montreal consensus. In conclusion, STin2 VNTR polymorphism of SLC6A4 gene may contribute to the pathogenesis of CD.

• Keywords: transporter za povratni unos serotonina; 5-HT; SERT; SLC6A4; 5-HTTLPR; rs25531; STin2 VNTR; Crohnova bolest
• Keywords (english): serotonin re-uptake transporter; 5-HTT; SERT; SLC6A4; 5-HTTLPR; rs25531; STin2 VNTR; Crohn’s disease
• Language: croatian
• URN:NBN: urn:nbn:hr:105:362612
• 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)
• Catalog URL: https://katalog.nsk.hr/F/19IT7Y755V1NXQJPHCLYSQGPF6BLAPPF179HQ7FAXXMYBYGMV5-27035?func=find-e&request=Povezanost+polimorfizama+gena+za+serotoninski+transportni+sustav+s+fenotipom+Crohnove+bolesti&find_scan_code=FIND_NAS&adjacent=N&local_base=MF_WEB&x=45&y=17&filter_code_1=WLN&filter_request_1=&filter_code_2=WYR&filter_request_2=&filter_code_3=WYR&filter_request_3=&filter_code_4=WFM&filter_request_4=
• Type of resource: Text
• Extent: 192 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-11-04 13:17:29