Associations of microRNAs, Angiogenesis-Regulating Factors and CFH Y402H Polymorphism-An Attempt to Search for Systemic Biomarkers in Age-Related Macular Degeneration

• Published in: International journal of molecular sciences 2019-11, Vol.20 (22), p.5750
• Main Authors: Ulańczyk, Zofia, Sobuś, Anna, Łuczkowska, Karolina, Grabowicz, Aleksandra, Mozolewska-Piotrowska, Katarzyna, Safranow, Krzysztof, Kawa, Miłosz Piotr, Pałucha, Andrzej, Krawczyk, Mariusz, Sikora, Piotr, Matczyńska, Ewa, Machaliński, Bogusław, Machalińska, Anna
• Format: Article
• Language: English
• Subjects: Age; Aged; Aged, 80 and over; amd; Angiogenesis; Bioinformatics; Biomarkers; Biomarkers - blood; Cell cycle; cfh; Female; Gene Frequency - genetics; Genomes; growth factors; Humans; Hypoxia; Intercellular Signaling Peptides and Proteins - metabolism; Macular degeneration; Macular Degeneration - blood; Macular Degeneration - genetics; Male; MicroRNAs; MicroRNAs - blood; mirna; Polymorphism; Polymorphism, Single Nucleotide - genetics; Vascular endothelial growth factor
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20225750

Age-related macular degeneration (AMD) remains the leading cause of blindness in elderly people, but the pathophysiology of this disease is still largely unknown. We investigated the systemic expression of angiogenesis-regulating growth factors and selected miRNAs known to regulate angiogenesis in AMD patients. We also focused on possible correlations of their expression with the presence of CFH Y402H or ARMS A69S risk variants. A total of 354 AMD patients and 121 controls were enrolled in this study. The levels of angiogenesis-regulating factors were analyzed in plasma samples using Luminex technology. The expression of selected miRNAs was analyzed in peripheral blood plasma using real-time qPCR. The genetic analysis was performed with an Illumina NextSeq500 system. AMD was an independent factor associated with lower levels of angiogenin (β = -0.29, < 0.001), endostatin (β = -0.18, < 0.001), FGF-basic (β = -0.18, < 0.001), PlGF (β = -0.24, < 0.001), miRNA-21-3p (β = -0.13, = 0.01) and miRNA-155-5p (β = -0.16, = 0.002); and with higher levels of FGF-acidic (β = 0.11, = 0.03), miRNA-23a-3p (β = 0.17, < 0.001), miRNA-126-5p (β = 0.13, = 0.009), miRNA-16-5p (β = 0.40, < 0.001), miRNA-17-3p (β = 0.13, = 0.01), miRNA-17-5p (β = 0.17, < 0.001), miRNA-223-3p (β = 0.15, = 0.004), and miRNA-93 (β = 0.11, = 0.04). The expression of analyzed miRNA molecules significantly correlated with the levels of tested angiogenesis-regulating factors and clinical parameters in AMD patients, whereas such correlations were not observed in controls. We also found an association between the CFH Y402H polymorphism and miRNA profiles, whereby TT homozygotes showed evidently higher expression of miRNA-16-5p than CC homozygotes or TC heterozygotes ( = 0.0007). Our results suggest that the balance between systemic pro- and anti-angiogenic factors and miRNAs is vital in multifactorial AMD pathogenesis.