495106632

konferencjach naukowych Warszawa 2019

Influence of polymorphisms in APOE, APOC1, and ACE genes on the risk of Alzheimer's disease

Marzena Skrzypa¹*, Natalia Potocka¹’, Halina Bartosik-Psujek²'³, Marcin Wiącek²'³,

Marcin Braun⁴, Izabela Zawlik¹*²*

'Laboratory of Molecular Biology, Centre for lnnovatrve Research m Medical and Natural Sciences, College of Medical Sciences, Unwersity of Rzeszów. Rzeszów. Poland >lnstitute of Experlmental and Cllmcal Mediclne. College of Medical Sciences, Unmerslty of Rzeszów. Rzeszów, Poland 'Clinical Department of Neurołogy Rzeszów State Hospital No. 2, Rzeszów, Poland ‘Department of Pathology, Chair of Oncology, Medical Unrversity of Lodź, 90-419 Lodź, Poland;

*Equal contnbution

•Correspondence author: Izabela Zawlik, email address: izazawllk<ą>yahoo.com

Backgraund: Alzheimcr’s disease (AD) is one of the most common neurodegonerath/e diseases, which is a serious health problem for socioties that llvc longcr. Polymorphisms of selected genes may play an important role in development of AD. Mild Cognitive Impairment (MCI) is considered an intermediate State between normal aging and dementia, mainly Alzheimer's type. The aim of this study was to assess the influence of polymorphisms of APOE, AP0C1, and ACE genes on the risk of AD. We examined the relationship between these gene polymorphisms (separately and in the followmg combinations: APOE and AP0C1, APOE and ACE and susceptibility to AD and MCI.

APOE gene (apolipoprotein E) has three ollclcs - e2, c3, e4 that encode the fdlowing isoforms: ApoE2, ApoE3 and ApoE4. Carriers of the E4 allele have an increased risk of developing Alzheimer’s. ApoE is a major lipid carrier and is involved in the clearance of the amyloid-beta (Ap) peptide from the brain. AP0C1 gene (apolipoprotein Cl) encodes ApoCl that is in partnership with apoE and participate with cholesterol metabolism, membranę remodeling, neuronal apoptosis and reorgamzation. ACE gene encodes angiotensin converting enzyme that is responsible for normal blood pressure. In vitro studies showed that ACE plays a role in Ap degradation.

Materials and methods: The study mcluded 63 patients with AD (mean age=74 88), 35 patients with MO (mean age=66.45) and 35 hcalthy subjects (mean age=66.05). DNA was isolated from WBC (White blood cells). Blood samples were taken from patients hospitalized in hospital No. 2 In Rzeszów. APOE and AP0C1 genotyplng was performed using PCR-RFLP methods. ACE insertion/dcletion (l/D) polymorphism was analyzed usmg PCR. For statistical analyses The Statistica 12.5 PL package (StatSoft, Tulsa, USA) was used.

Results: The representativeresultsof polymorphism are shown in Figurę 1. We observed a very strong correlation between the presence of APOE e4 and AP0C1II (insertion/insertion) and ID (insertion/deletion) genotypes and the risk of MCI and AD development shown in Table 1 and Table 2.

ll| : Agarot* |*l •l»<trophorMog>»"ufc< polrmorphiunaftłtyut.

IA) KA *t*C-ert tńAPOt mm iepar»t**y dgetted wrth twp rłitnctloo łrzymes Afl ■ and Ha* • Th* 218 bp *CA pcodutt ot <l**v«d by ATI ll Into 168 *nd SO bp Th* *C* ptoduct ot «lłOdi|»it*d with n*« I mto 19S bp »nd 21 bp |th* 21 bp n ty Polly rot ylwtl* on th* g*ty|.Th* band panam lot g*notyp*t: 2/2 -148. SO and 218 bp: 2/1 -168. SO and 218. 19S. 21 bp. 2/4 • 2ł«. JM. SO *nd 211 1 W. 2 J bp. 1/1 - 148. SO «rd IW. 21 bp. 1/4 - 21*. 168. SO *rd ; W. 21 bp: 4/4- 218 and IW, 21 bp ra«pactrv*»y tor łtwyrwt AJ# NI *rdH»« i

(81 Th* *C# *nplitl*<lli*C^,*nt oTATOCZ »*l WbKCttd to    with Hp* I Th* 1(9 bp *C* product w*>cl«*r«d irAo two fr«*m*wttO1118 *nd SI bp lot I genotyp*. th<ee fragment* of 169. 118 and SI bpfer >0 C*"0ttp*. wh.le th* 00

homorygowl ramalned uncl**ved Ihowlnf orły th* 149 bp *C* product (Cl Th* *c« ptoduct 0> ACl <t 480 bpłot II genotyp*, two K* productt o( 480 *nd 191 bp ter 10 genotyp*, wtul* 191 bp ter OOgenotyp*

MM- molecul*' w* rtłrtwt |S01. 404. 111. 242. 190. 147.111. *7 bpi. »9C« • KA ptoduct contro!. <N - r*g.ti,e contro! *CR fragmanti i»pa"»l»d on 21N ygi-cty gala

C

“"mmm+m" i

i— - —•¹

Tłble 1 Alzheimer drtease APOl vs AP0<1 - very strong reutionthp w the whde group ix 0.00001
	APOC1	APOCf	APOC1
	DD	ID	II
APOE 3\3	31 (51*)	1(2*)	0(0*)
APOE 213	1(2*)	1(2*)	0(0*)
APOE 3\4	2(3*)	17(28*)	0(0*)
APOE 4A	0(0*)	0(0*)	5(8*)
APOE TA	0(0*)	0(0*)	3(5*)

T*ble2. MCI • APOt vt. APOC1 • wy strong rełatłeoshlp in th* wttoie MO _ group pcO OOOOl

	APOCf DO	APOCf ID	APOCf II
APOE30	19(66*)	1(3*)	0(0*)
APOE20	0(0*)	1(3*)	0(0*)
APOE3A	0(0*)	5(17*)	0(0*)
APOE4A	0(0*)	0(0*)	1(3*)
APOE TA	0(0*)	0(0*)	1(3*)

We shown the relationship between the age of diagnosis of MCI or AD and the genotype in the APOE gene (Fig. 2). Moreover, a similar relationship was obseryed between the age of diagnosis of MCI or AD and the genotype in the APOC1 gene (Fig. 3)

We also observed that people with DD (deletion/deletion) genotype in the ACE gene were diagnosed MCI at a later age (Fig. 4)

RM

Condusion: This results suggest the APOC1 insertion allele, in combination with APOE £4, may be a potential risk factor for developing AD. Moreover, the ACE polymorphism may influence on MCI age of onset.

FUNDING SOURCE: This study was supported by the Uniyersity of Rzeszów.

Warsaw Neuropathology Neurogenetics 2019

pt.com