Possible Protective Effect of LOXL1 Variant in the Cohort of Chernobyl Catastrophe Clean-Up Workers

• Published in: Genes Vol. 12; no. 8; p. 1231
• Main Authors: Žukauskaitė, Gabrielė, Domarkienė, Ingrida, Matulevičienė, Aušra, Vaitėnienė, Evelina Marija, Arasimavičius, Justas, Smailytė, Giedrė, Kučinskas, Vaidutis, Ambrozaitytė, Laima
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.08.2021; MDPI
• Subjects: Alleles; Amino Acid Oxidoreductases - genetics; Case-Control Studies; Chernobyl Nuclear Accident; Chromosomes; Cohort Studies; Connective tissue; Disasters; Environmental factors; Epistasis; Equilibrium; Exfoliation; Genetic analysis; Genomes; Genomics; Genotype & phenotype; Genotypes; Genotyping; Glaucoma; Humans; Linkage analysis; Linkage Disequilibrium; Male; Occupational Exposure; Phenotypes; Population; Positive selection; Quality control; Questionnaires; Risk factors; Single-nucleotide polymorphism; Software; Statistical analysis; Ukraine; Ukraine; United States > US; exfoliation syndrome; protective genome variant; Lithuanian population; glaucoma; Chernobyl nuclear disaster; genome-wide association study; LOXL1
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12081231

Ionising radiation (IR) is an environmental factor known to alter genomes and therefore challenge organisms to adapt. Lithuanian clean-up workers of the Chernobyl nuclear disaster (LCWC) experienced high doses of IR, leading to different consequences. This study aims to characterise a unique protective genomic variation in a relatively healthy LCWC group. This variation influenced their individual reaction to IR and potentially protects against certain diseases such as exfoliation syndrome and glaucoma. Clinical and IR dosage data were collected using a questionnaire to characterise the cohort of 93 LCWC. Genome-wide genotyping using Illumina beadchip technology was performed. The control group included 466 unrelated, self-reported healthy individuals of Lithuanian descent. Genotypes were filtered out from the microarray dataset using a catalogue of SNPs. The data were used to perform association, linkage disequilibrium, and epistasis analysis. Phenotype data analysis showed the distribution of the most common disease groups among the LCWC. A genomic variant of statistical significance (Fishers' exact test, 0.019), rs3825942, was identified in (NM_005576.4:c.458G>A). Linkage disequilibrium and epistasis analysis for this variant identified the genes , , , , and as potentially involved in the etiopathogenesis of exfoliation syndrome and glaucoma, which were not previously associated with the disease. The variant is mostly considered a risk factor in the development of exfoliation syndrome and glaucoma. The influence of recent positive selection, the phenomenon of allele-flipping, and the fact that only individuals with the homozygous reference allele have glaucoma in the cohort of the LCWC suggest otherwise. The identification of rs3825942 and other potentially protective genomic variants may be useful for further analysis of the genetic architecture and etiopathogenetic mechanisms of other multifactorial diseases.