Vpliv polimorfizmov apolipoproteina E in elementov v sledovih na antioksidativni status žensk v rodni dobi

France Štiglic, Alenka (author), Marc, Janja (mentor), Falnoga, Ingrid (comentor)

Uvod: Izooblike apolipoproteina E (apoE; gen APOE), ki izhajajo iz genskih različic ɛ2, ɛ3 in ɛ4, različno vplivajo na presnovo lipidov in oksidativno stanje (OS) ter na elemente v sledovih (TE). Razlike so lahko pomembne pri bolezenskih stanjih ali fizioloških procesih, kot sta sposobnost zanositve in nosečnost. Metode: V raziskavo smo vključili 172 zdravih žensk v rodni dobi in jih razdelili v tri genotipske skupine APOE: APOE3 (ɛ3/ɛ3), APOE4 (ɛ3/ɛ4 in ɛ4/ɛ4) in APOE2 (ɛ2/ɛ2 in ɛ2/ɛ3). OS smo ovrednotili z merjenjem celotne antioksidativne zmogljivosti plazme, encimov SOD1, GPx1 in katalaze v eritrocitih ter 8-izoprostana in 8-hidroksideoksigvanozina v urinu. Sedemnajst TE smo v krvi, plazmi, eritrocitih in urinu določili z ICP-MS. Hkrati smo z analizo TE v krvi 192 zdravih krvodajalcev določili nacionalne referenčne intervale za merjene TE. Povezave med genotipi APOE, TE in parametri OS smo ocenjevali z linearnimi regresijskimi modeli z več neodvisnimi spremenljivkami, pri tem smo upoštevali socialnodemografske in antropometrične značilnosti ter dejavnike življenjskega sloga. Ob povezavah z genotipi APOE smo preverili tudi vpliv izbranih TE na označevalce OS. Rezultati: Vrednosti TE in označevalcev OS preiskovank so bile v območju referenčnih vrednosti za splošno populacijo. Prisotnost alela ɛ4 je bila povezana s statistično značilno višjimi vrednostmi 8-izoprostana (do 54,2 %) v primerjavi s ɛ3/ɛ3. Opazili smo majhen (do –1,1 %), vendar pomemben zaščitni vpliv posameznih esencialnih TE pri nastanku 8-izoprostana. Pri drugih parametrih OS ni bilo izraženih razlik glede na genotipe. Zaključek: Genotip APOE4 je bil jasno povezan z višjimi vrednostmi označevalca lipidne peroksidacije, 8-izoprostana. Povečana lipidna peroksidacija prek območja fiziološke variabilnosti lahko neugodno vpliva na plodnost in nosečnost, pri nosilkah ɛ4 pa lahko zmanjša znano prednost ugodnejšega hormonskega stanja pri zanositvi. Ti izsledki lahko podprejo nacionalne epidemiološke študije o rodnosti in so izhodišče za nadaljnje temeljne raziskave interakcij med geni in okoljem, ki vplivajo na OS.

• Language: Slovenian
• Keywords: genotipi APOE, elementi v sledovih, oksidativno stanje, linearni regresijski modeli z več spremenljivkami, človek, 8-izoprostan, 8-hidroksideoksigvanozin, superoksidna dismutaza 1, glutationska peroksidaza 1, katalaza
• Work type: Doctoral dissertation
• Typology: 2.08 - Doctoral Dissertation
• Organization: FFA - Faculty of Pharmacy
• Publisher: [A. F. Štiglic]
• Year: 2025
• PID: 20.500.12556/RUL-184988
• UDC: 577.21(043.3)
• COBISS.SI-ID: 268402947
• Publication date in RUL: 20.07.2026

Secondary language

• Language: English
• Title: The impact of apolipoprotein E gene polymorphism and trace elements on the antioxidant status of women in childbearing age

Abstract

Background: Apolipoprotein E (apoE; gene APOE) exists in three major isoforms: ɛ2, ɛ3, and ɛ4. These variants have distinct effects on lipid metabolism and oxidative status (OS), potentially influencing trace element (TE) concentrations. Such differences can be especially relevant in specific health conditions or physiological processes, such as fertility and pregnancy. Methods: The study included 172 healthy women of reproductive age. Participants were grouped into three APOE genotype categories: APOE3 (ɛ3/ɛ3), APOE4 (ɛ3/ɛ4 and ɛ4/ɛ4), and APOE2 (ɛ2/ɛ2 and ɛ2/ɛ3). OS was assessed through plasma total antioxidant capacity, erythrocyte antioxidant enzymes (SOD1, GPx1, and catalase), and urinary markers 8-isoprostane and 8-hydroxy-2'-deoxyguanosine. Seventeen TE were measured in blood, plasma, erythrocytes, and urine using ICP-MS. Simultaneously, we established national reference intervals for the measured trace elements based on a cohort of 192 healthy blood donors. Associations among APOE genotypes, TE, and OS markers were analysed using multivariable linear regression models, adjusting for sociodemographic and anthropometric characteristics as well as lifestyle factors. The influence of selected TE on the associations between APOE genotypes and oxidative status markers was also examined. Results: TE and oxidative status marker levels were within reference ranges for the general population. Carriers of the ɛ4 allele showed significantly higher urinary 8-isoprostane levels (up to +54.2%) compared to ɛ3/ɛ3. A modest (up to –1.1%) yet statistically significant protective effect of individual essential trace elements on 8-isoprostane formation was observed. Other OS markers showed no significant differences between genotypes. Conclusion: The APOE4 genotype was strongly associated with elevated levels of 8-isoprostane, a non-enzymatic marker of lipid peroxidation. This increase beyond normal physiological variability may negatively affect fertility and pregnancy, potentially counteracting the hormonal advantages typically observed in ɛ4 carriers. These findings may support national epidemiological studies on fertility and provide a basis for future research on gene-environment interactions that influence OS.

• Keywords: APOE genotypes, Trace elements, Oxidative status, Multiple variable linear regression models, 8-isoprostane, 8-hydroxy-2-deoxyguanosine, superoxide dismutase 1, glutathione peroxidase 1, catalase