Vztah mezi Alzheimerovou chorobou a polymorfizmy kandidátních genů

Bc. Miroslav Bardelčík

Master's thesis

The relationship between Alzheimer's disease and candidate gene polymorphisms

Abstract:

This diploma thesis deals with the association study of selected polymorphisms in APOE and ALOX5AP genes (polymorphism rs4769874) and the risk of Alzheimer's disease. This study includes 1083 persons from Czech Republic, 726 of them have suffered of AD and 357 were included as verification subjects. In case of polymorphism rs405509 of gene for APOE it was found that genotype CC in contrast to AA, decrease the risk of AD. Combined risk study identified that combined genotype isoforms of gene for APOE / rs4055509 - E3E4 AA (p < 0,001), E3E4 AC (p < 0,001), E4E4 AA (p < 0,02) and genotype E4E4 AC (p < 0,03) increase the risk of AD. It was confirmed in the study of the genotype of APOE gene isoform, that allele E4 is one of risk factor – allele E4 increases the risk of AD 2,31x and genotype E4E4 increases the risk of AD 3,49x. Association study of rs4769874 polymorphism did not confirm a statistically significant association with AD, however some relationships between combined APOE isoforms and the risk of AD were found.

Abstract:

Táto diplomová práca sa zaoberá asociačnou štúdiou vzťahu medzi polymorfizmami génu pre APOE a ALOX5AP (polymorfizmus rs4769874) a rizikom Alzheimerovej choroby (AD). Štúdia zahrňovala 1083 osôb, z toho 726 osôb trpiacich AD a 357 kontrolných osôb z Českej republiky. V prípade polymorfizmu rs4055090 génu pre APOE bolo zistené, že genotyp CC, oproti AA, znižuje riziko AD. Pri štúdií kombinovaných rizík bolo zistené, že kombinované genotypy izoformy APOE / rs405509 - E3E4 AA (p < 0,001), E3E4 AC (p < 0,001), E4E4 AA (p < 0,02) a genotyp E4E4 AC (p < 0,03) zvyšujú riziko AD. Pri študovaní genotypových izoforiem génu pre APOE bolo potvrdené, že alela E4 patrí medzi rizikové faktory – alela E4 zvyšuje riziko AD 2,31x a genotyp E4E4 zvyšuje riziko 3,49x. Asociačná štúdia polymorfizmu rs4769874 génu pre ALOX5AP nepotvrdila štatisticky významnú asociáciu s AD, ale boli zistené niektoré kombinované riziká s izoformou APOE a s rizikom ochorenia AD.

Keywords

Alzheimerova choroba, Apolipoproteín E, Arachidonát 5-lipoxygenázový aktivační proteín, Amyloid β, Tau proteín, Asociačná štúdia, Jednonukleotidový polymorfizmu

Language used: Slovak

Date on which the thesis was submitted / produced: 15. 5. 2017

Thesis defence

• Date of defence: 7. 6. 2017
• Supervisor: prof. RNDr. Omar Šerý, Ph.D.

Masaryk University

Faculty of Science

Master programme / field:
Biochemistry / Analytical Biochemistry