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Piotr Krawczyk, Jean-Marc Perone, anna ambroziak, joanna giebultowicz, Oualid Guechi, adina agapie, Nadia OUAMARA, Louis Lhuillier, Naïla Houmad, Huong Duong Nguyen Viet, jacek szaflik; Is keratoconus risk associated with genetic variation of aldehyde dehydrogenase ALDH3A1 gene?. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2905.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the influence of the genetic variation of the ALDH3A1 gene region on the risk of keratoconus in the European population. ALDH3A1 is a structural and enzymatic protein representing up to 50% of the corneal water-soluble proteins in mammalian species, which may be involved in the pathogenesis of keratoconus.
The study, conducted at the Department of Ophtalmology at the Medical Universitity of Warsaw, consisted of sequencing of promotor regions, 10 exons and intronic sequences flanking each exon of the ALDH3A1 gene. A total of 300 keratoconus patients were examined (EDTA blood samples). Patients with any metabolic defects were excluded. DNA isolation was performed with the kit method followed by a polymerase chain reaction (PCR). A direct sequencing of all exons ALDH3A1 and/or analysis of important gene rearrangements were performed. Direct fluorescent sequencing (Applied Biosystems 3130 Genetic Analyzer) was applied to screen any gene mutations in patients DNA. The frequencies of selected SNPs in the control group were checked using high resolution melt technique (HRM) or TaqMan technique (StepOne Plus Real-Time PCR System AppliedBiosystem). Programs like SNPSplicer, EuSplice, GeneSplicer and ESE Finder were used to verify and analyze a potential impact of sequence variation on pre-mRNA splicing.
Our results were compared with data from the European population genomic base (phase 1 of the 1000 Genomes Projects). According to our analysis, three single nucleotide polymorphisms SNPs are in linkage disequilibrium (D’= 0,916-1, r2=0,727-0,93) and are organized in haplotype block. The study did not show any punctual mutations in the analyzed aldehyde dehodrogenase ALDH3A1 region, however our analysis confirmed the existence of ten already known single nucleotide polymorphisms (SNPs) in the examined area.
The study results show that keratoconus does not seem to be associated with any mutation in the ALDH3A1 gene region. However, the proven presence of single nucleotide polymorhisms SNPs in the analyzed zone requires further attention and probably plays a considerable role in the risk and prevalence of this pathology.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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