Title Učestalost polimorfizama gena AGT, ACE, AGTR1, ADRB1, UMOD i ADIPOQ u osoba s predhipertenzijom
Title (english) Frequency of AGT, ACE, AGTR1, ADRB1, UMOD and ADIPOQ Genetic Polymorphisms in Prehypertension
Author Livija Šimičević
Mentor Bojan Jelaković (mentor)
Mentor Jasna Lovrić (komentor)
Committee member Živka Dika (predsjednik povjerenstva)
Committee member Dunja Rogić (član povjerenstva)
Committee member Nada Božina (član povjerenstva)
Granter University of Zagreb School of Medicine (Department of Internal 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 Arterijska hipertenzija (AH) je glavni nezavisni čimbenik rizika za kardiovaskularnu (KV) i cerebralnu smrtnost i pobole i jedan je od glavnih čimbenika rizika kronične bubrežne bolesti. Predhipertenzija (PHT) tj. visoko normalan arterijski tlak (AT) također je povezana s KV rizikom i rizikom od progresije u AH. Dosadašnja istraživanja genske podloge predhipertenzije su nedostatno provedena, a rezultati ukazuju na moguću povezanost određenih gena uključenih u etiopatogenezu AH i PHT. Manjkavost i ponekad inkonzistentnost informacija i rezultata o ulozi polimorfizama gena u etiopatogenezi PHT bili su poticaj ovom istraživanju. Naša hipoteza bila je da se polimorfizmi rs2004776 AGT, rs1799752 ACE, rs5196 AGTR1, rs1801253 ADRB1, rs13333226 UMOD te rs266729 i rs17300539 ADIPOQ, koji su povezani s AH i metaboličkim sindromom, učestalije nalaze u osoba s visoko normalnim AT tj. predhipertenzijom nego u osoba s optimalnim i normalnim AT. Odabrali smo ove polimorfizme jer su ti geni uključeni u razne mehanizme koji dovode do porasta AT i metaboličkih komplikacija.
U ovo presječno, opservacijsko istraživanje je uključen 601 ispitanik; 319 s visoko normalnim AT (PHT, 120/80–139/89 mmHg), oba spola, dobi 20 – 45 godina, te 282 ispitanika s normalnim i optimalnim AT kao kontrolna skupina (NT).
Rezultati su pokazali da se istraživani polimorfizmi gena ne nalaze učestalije u skupini PHT nego u NT. Međutim, ustanovljena je značajno manja učestalost heterozigotnoga genotipa rs266729 ADIPOQ u PHT (35,1 %), u usporedbi s učestalosti u NT (44,7 %), P= 0,03. Izgled za pojavu PHT je 0,66 puta manji u heterozigotnih (C/G) nositelja rs266729 ADIPOQ. Dokazali smo značajnu povezanost minor alela G rs13333228 UMOD s nižim vrijednostima sistoličkoga i dijastoličkoga AT i minor alela A rs17300539 ADIPOQ s nižim vrijednostima sistoličkoga AT. Dodatno, naše istraživanje je rezultiralo određivanjem dva haplotipa koji su značajno pozitivno povezani s nastankom PHT. Prvi je hIAGC s 41 % većom vjerojatnosti za pojavu PHT (rs1799752 ACE + rs13333226 UMOD + rs17300539 ADIPOQ + rs266729 ADIPOQ). Učestalost ovoga haplotipa za 8 % veća u PHT nego u NT. Drugi haplotip je hIAGCA i ima 47 % veću vjerojatnost za pojavu PHT (rs1799752 ACE + rs13333226 UMOD + rs17300539 ADIPOQ + rs266729 ADIPOQ + rs5186 AGTR1). Učestalost hIAGCA u NT je 18 %, dok je u PHT 23 %. Nadalje, značajan je i nalaz modela multivarijantnoga predviđanja PHT (interakcija gen – gen – ostali određivani parametri) koji uključuje pro-predhipertenzivni značajan učinak muškoga spola, tjelesne mase, frekvencije srca, koncentracije glukoze na tašte i ukupnoga kolesterola, dok zaštitno djelovanje unutar ovog modela imaju tjelesna visina i heterozigotni (G/A) genotip rs17300539 ADIPOQ. Ukazali smo na mogući značaj gena koji kodiraju proteine uključene u bitne biološke puteve odgovorne za kontrolu AT, koji između ostalih obuhvaćaju renin-angiotenzin-aldosteronski sustav, bubreg, središnji živčani sustav, krvožilje kao i masno tkivo.
Zaključno, provedenim analizama potvrdili smo i pokazali prisutnost značajnih interakcija gen – gen i gen – ostali određivani parametri (antropometrijski, biokemijski, okolišni čimbenici), ali i interakcija gen – gen – ostali određivani parametri u etiologiji PHT.
Abstract (english) Arterial hypertension (AH) is a major independent risk factor for cardiovascular (CV) and cerebral mortality and morbidity and is one of the major risk factors for chronic kidney disease. Prehypertension (PHT) i.e. high normal arterial pressure (AP) is also associated with CV risk and risk of progression in AH. Previous studies of the genetic background of PHT have been insufficiently conducted, and the results indicate a possible association of certain genes involved in the etiopathogenesis of AH and PHT. The lack and sometimes inconsistency of information and results on the role of gene polymorphisms in the etiopathogenesis of PHT were the impetus to this research. Our hypothesis was that polymorphisms rs2004776 AGT, rs1799752 ACE, rs5196 AGTR1, rs1801253 ADRB1, rs13333226 UMOD and rs266729 and rs17300539 ADIPOQ, which are associated with AH and metabolic syndrome, are more common in individuals with high normal AP i.e. prehypertension than in individuals with optimal and normal AP. We chose these polymorphisms because these genes are involved in various mechanisms that lead to an increase in AP and metabolic complications.
In this cross-sectional, observational study, 601 subjects were included; 319 with high normal AP (PHT, 120/80–139/89 mmHg), both sexes, aged 20–45 years, and 282 subjects with normal and optimal AP as a control group (NT).
The results showed that the investigated gene polymorphisms are not found more frequently in the PHT group than in the NT. However, a significantly lower frequency of the heterozygous genotype rs266729 ADIPOQ was found in PHT (35.1%), compared to the frequency in NT (44.7%), P = 0.03. The incidence of PHT is 0.66-fold lower in heterozygous (C/G) carriers of rs266729 ADIPOQ. We demonstrated a significant association of the minor allele G rs13333228 UMOD with lower values of systolic and diastolic AP and the minor allele A rs17300539 ADIPOQ with lower values of systolic AP. Additionally, our study resulted in the identification of two haplotypes that were significantly positively associated with PHT formation. The first is hIAGC with a 41% higher probability of developing PHT (rs1799752 ACE + rs13333226 UMOD + rs17300539 ADIPOQ + rs266729 ADIPOQ). The frequency of this haplotype is 8% higher in PHT than in NT. The second haplotype is hIAGCA and is 47% more likely to develop PHT (rs1799752 ACE + rs13333226 UMOD + rs17300539 ADIPOQ + rs266729 ADIPOQ + rs5186 AGTR1). The frequency of hIAGCA in NT is 18%, while in PHT it is 23%. Furthermore, the finding of a model of multivariate prediction of PHT (gene-gene-other determined parameters interaction) which includes a pro-prehypertensive significant effect of male sex, body weight, heart rate, fasting glucose concentration and total cholesterol is significant, while the protective effect within this model have body height and heterozygous (G/A) genotype rs17300539 ADIPOQ. We pointed to the possible importance of genes encoding proteins involved in essential biological pathways responsible for AP control, which include, among others, the renin-angiotensin-aldosterone system, the kidney, the central nervous system, blood vessels, and adipose tissue.
In conclusion, the performed analyzes confirmed and showed the presence of significant gene - gene and gene - other determined parameters interactions (anthropometric, biochemical, environmental factors), but also gene - gene - other determined parameters in the etiology of PHT.
Keywords
predhipertenzija
genski polimorfizam
AGT
ACE
AGTR1
ADRB1
UMOD
ADIPOQ
Keywords (english)
prehypertension
gene polymorphism
AGT
ACE
AGTR1
ADRB1
UMOD
ADIPOQ
Language croatian
URN:NBN urn:nbn:hr:105:034289
Project Number: 108-0000000-0329 Title: ENDEMSKA NEFROPATIJA U HRVATSKOJ, epidemiologija, dijagnostika i etiopatogeneza Title: ENDEMIC NEPHROPATHY IN CROATIA, epidemiology, diagnosis, etiopathogenesis Leader: Bojan Jelaković Jurisdiction: Croatia Funder: MZOS Funding stream: ZP
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/19IT7Y755V1NXQJPHCLYSQGPF6BLAPPF179HQ7FAXXMYBYGMV5-31037?func=find-e&request=U%C4%8Destalost+polimorfizama+gena+AGT%2C+ACE%2C+AGTR1%2C+ADRB1%2C+UMOD+i+ADIPOQ+u+osoba+s+predhipertenzijom&find_scan_code=FIND_NAS&adjacent=N&local_base=MF_WEB&x=0&y=0&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=
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Created on 2021-03-10 09:36:20