Dataset Information

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

ABSTRACT: 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 (? = -0.29, p < 0.001), endostatin (? = -0.18, p < 0.001), FGF-basic (? = -0.18, p < 0.001), PlGF (? = -0.24, p < 0.001), miRNA-21-3p (? = -0.13, p = 0.01) and miRNA-155-5p (? = -0.16, p = 0.002); and with higher levels of FGF-acidic (? = 0.11, p = 0.03), miRNA-23a-3p (? = 0.17, p < 0.001), miRNA-126-5p (? = 0.13, p = 0.009), miRNA-16-5p (? = 0.40, p < 0.001), miRNA-17-3p (? = 0.13, p = 0.01), miRNA-17-5p (? = 0.17, p < 0.001), miRNA-223-3p (? = 0.15, p = 0.004), and miRNA-93 (? = 0.11, p = 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 (p = 0.0007). Our results suggest that the balance between systemic pro- and anti-angiogenic factors and miRNAs is vital in multifactorial AMD pathogenesis.

SUBMITTER: Ulanczyk Z

PROVIDER: S-EPMC6887747 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Ulańczyk Zofia Z Sobuś Anna A Łuczkowska Karolina K Grabowicz Aleksandra A Mozolewska-Piotrowska Katarzyna K Safranow Krzysztof K Kawa Miłosz Piotr MP Pałucha Andrzej A Krawczyk Mariusz M Sikora Piotr P Matczyńska Ewa E Machaliński Bogusław B Machalińska Anna A

International journal of molecular sciences 20191115 22

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 ...[more]

PMID: 31731799

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Project description:To examine if the gene encoding C-reactive protein (CRP), a biomarker of inflammation, confers risk for neovascular age-related macular degeneration (AMD) in the presence of other modifiers of inflammation, including body mass index (BMI), diabetes, smoking, and complement factor H (CFH) Y402 genotype. Additionally we examined the degree to which CRP common variation was in linkage disequilibrium (LD) within our cohort.We ascertained 244 individuals from 104 families where at least one member had neovascular AMD, and a sibling had normal maculae and was past the age of the index patient's diagnosis of neovascular AMD. We employed a direct sequencing approach to analyze the 5'-promoter region as well as the entire coding region and the 3'-untranslated region of the CRP gene. CFH Y402 genotype data was available for all participants. Lifestyle and medical factors were obtained via administration of a standardized questionnaire. The family-based association test, haplotype analysis, McNemar's test, and conditional logistic regression were used to determine significant associations and interactions. Haploview was used to calculate the degree of LD (r2) between all CRP variants identified.Six single nucleotide polymorphisms (SNPs; rs3091244, rs1417938, rs1800947, rs1130864, rs1205, and rs3093068) comprised one haplotype block of which only rs1130864 and rs1417938 were in high LD (r2=0.94). SNP rs3093068 was in LD but less so with rs3093059 (r2=0.83), which is not part of the haplotype block. Six SNPs made up six different haplotypes with > or = 5% frequency, none of which were significantly associated with AMD risk. No statistically significant association was detected between any of the nine common variants in CRP and neovascular AMD when considering disease status alone or when controlling for smoking exposure, BMI, diabetes, or CFH genotype. Significant interactions were not found between CRP genotypes and any of the risk factors studied. No novel CRP variation was identified.We provide evidence that if elevated serum/plasma levels of CRP are associated with neovascular AMD, it is likely not due to genetic variation within CRP, but likely due to variations in some other genetic as well as epidemiological factors.

Dataset Information

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

Publications

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

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