Učestalost genotipova ABO sustava krvnih grupa u oboljelih od tromboembolija u Hrvatskoj

doctoral thesis

• Title (english): Distribution of ABO genotypes among patients with thromboembolism in Croatia
• Author: Irena Jukić
• Mentor: Jasna Bingulac-Popović (mentor); MBZ: 177071
• Committee member: Renata Zadro (predsjednik povjerenstva)
• Committee member: Mirna Sučić (član povjerenstva)
• Committee member: Ana-Maria Šimundić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2013-02-05, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Brojna istraživanja u posljednjih desetak godina usmjerena su otkrivanju biološke uloge sustava
krvnih grupa, te su i pokazala veću ili manju povezanost između ABO sustava krvne grupe i nekih bolesti, kao
što su kardiovaskularne, gastrointestinalne, tumorske i infektivne. Tromboembolijske bolesti su veliki
javnozdravstveni problem i jedan od vodećih uzroka mortaliteta populacije. Zbog toga je od velikog značenja
utvrditi čimbenike rizika koji su uključeni u razvoj ovih bolesti, kako bi mogli spriječiti nastanak, ponavljanje
trombotičkih epizoda i poboljšati liječenje. Poznato je da nositelji ne-O krvne grupe ABO sustava imaju
povećani trombotički rizik. Razlika između O i ne-O KG je u razini glikoproteina von Willebrand u plazmi koja
je za 25-30% niža kod osoba s O krvnom grupom, u odnosu na ne-O krvne grupe. Smatra se da je to posljedica
izravnog funkcionalnog utjecaja ABO genskog !okusa, ali mehanizam nije razjašnjen.
Cilj istraživanja bio je utvrditi povezanost ABO genotipova i genetičkih protrombotičkih čimbenika
kao genetičkih čimbenika rizika za razvoj tromboze (FV Leiden, protrombin 02021 OA i metilentetrahidrofolat
reduktaza C677T) u hrvatskoj populaciji.
Istraživanjem je obuhvaćeno 164 bolesnika s venskom trombozom, 182 bolesnika s arterijskom trombozom i 303
asimptomatska dobrovoljna davatelja krvi koji su predstavljali kontrolnu skupinu.Genotipizacija na 5 osnovnih
alela i 15 genotipova bila je izvedena pomoću PCR-SSP metode, protrombotičke mutacije nac:injene su pomoću
metoda PCR-SSP, PCR-RFLP i RT-PCR.
Dobiveni rezultati ovog istraživanja pokazuju povećani trombotički rizik kod ne-00 nositelja u odnosu
na 00 nositelje genotipova za razvoj tromboembolijskih bolesti. Utvrđen je veći rizik za obolijevanje od
tromboembolijskih bolesti kod nositelja genotipova 01B/02B/BB i AB/ A2B tj. A i B alela, gdje bolesnici imaju
povećanu rizik za VTE u odnosu na nositelje 00 alela. Kod infarkta miokarda niti jedan ne-00 genotip ne
povećava trombotički rizik. Mutacija FVL u skupini ne-00 nositelja povećava izglede za razvoj venske
tromboze oko 9 puta, za nositelje MTHFR 677TT povećava ih za oko 4 puta, dok mutacija FII 02021 OA kod ne-
00 nositelja kao čimbenik rizika nema značenje. Protrombotički genetički čimbenici niti u jednoj skupini ne
doprinose povećanju rizika za razvoj arterijske tromboembolije, tj. akutnog infarkta miokarda.
Rad predstavlja temelje za istraživanje ABO sustava krvnih grupa kao genetičkog čimbenika rizika za
druge kardiovaskularne bolesti, kao i gastrointestinalne, tumorske i infektivne bolesti.

Abstract (english)

These decades numerous researches were directed to detection of biological function of blood group systems.
There have been reports on a lower or higher association between ABO blood groups and cardiovascular,
tumour, gastrointestinal, and infectious diseases. Thromboembolic diseases are important public health problem
and one ofleading cause ofpopulation mortality. It is ofutmost importance to identify the risk factors implicated
in the disease development. Most studies performed to date have generally agreed that non-00 blood group
carriers have a higher risk of thrombosis than 00 blood group carriers. Differences between O and non-0
blood groups are in values of glycoprotein von Willebrand factor in plasma which is by 25-30% lower in O
blood group than in non-0 blood group. The hypothesis is that this occurs due to the direct functional impact of
ABO locus; however, the exact mechanism bas not yet been elucidated.
Aim of the study was to assess the association between ABO blood group genotypes and genetic risk
factors for thrombosis (FV Leiden, prothrombin G202 l OA, and methylenetetrahydrofolate reductase C677T
mutations) in the Croatian population. The study included 164 patients with VTE, 182 patients with CAD and
303 asymptomatic blood donors as a control group. Genotyping to 5 common alleles and 15 genotypes was
performed by PCR-SSP and prothrombotic mutations were determined by PCR-SSP, PCR-RFLP and RT-PCR
methods.
The results show higher thrombotic risk for non-00 carriers compared to 00 genotype carriers for the
development of thromboembolic diseases. The strongest association with thrombotic risk was recorded for
OIB/02B/BB andi AB/ A2B; carriers of A and B allele have highest VTE risk than 00 allele carriers. There
was no significant difference between genotypes in the risk of myocardial infarction. FV Leiden increased the
risk of thrombosis 9-fold in the group of non-00 carriers, and fourfold in the group of MTHFR 677TT
carriers, while there was no significant difference in the risk of thrombosis between 00 and non-00 blood
groups associated with prothrombin mutation. There was no contribution of prothrombotic genetic factors to
risk for development of myocardial infarction.
Study represents a basis for research of ABO blood group system as genetic risk factors for other
cardiovascular diseases, as well as gastrointestinal, cancer and infectious diseases.

• Keywords: ABO krvne grupe; tromboembolije; tromboza; ABO genotipovi
• Keywords (english): ABO blood groups; thromboembolism; thrombosis; ABO genotypes
• Language: croatian
• URN:NBN: urn:nbn:hr:163:569749
• Study programme: Title: Pharmacy and biochemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor znanosti (doktor znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2016-11-28 14:59:52