Association of single nucleotide variants in the COL5A1 gene and adjacent intergenic space with keratoconus in a cohort of patients from Russia

• Published in: Oftalʼmokhirurgii͡a︡ = Ophthalmosurgery no. 1; pp. 6 - 13
• Main Authors: Skorodumova, L.O., Belodedova, A.V., Zakharova, E.S., Sharova, E.I., Bikbov, M.M., Usubov, E.L., Antonova, O.P., Malyugin, B.E.
• Format: Journal Article
• Language: English; Russian
• Published: Publishing house "Ophthalmology" 01.04.2020
• Subjects: keratoconus, col5a1, genetic markers, diagnosis
• ISSN: 0235-4160; 2312-4970
• DOI: 10.25276/0235-4160-2020-1-6-13

Purpose. To assess an association of markers near the COL5A1 gene and in its intron with keratoconus. To study the relationship between the presence of marker alleles and the level of expression of the COL5A1 gene in the cornea of patients with keratoconus.Material and methods.The study included 70 patients diagnosed with keratoconus, and 100 participants of the control group. All participants were genotyped for two markers associated with keratoconus: rs1536482 and rs7044529. The diagnostic indicators were calculated to assess a possibility of application of these markers as a keratoconus classifiers. In patients with keratoconus who underwent keratoplasty, corneal samples (n=9) were collected to isolate the RNA. The COL5A1 gene expression level was compared between the group of patient corneal samples with at least one marker allele (rs1536482 +) and the group of samples without marker alleles (rs1536482-) using real-time PCR coupled with reverse transcription.Results. A significant difference of the rs1536482 marker allele occurrence was found between the group of keratoconus patients and the control group (p=0.0004, Fisher test). At least one marker allele rs1536482 was found in 67.1% of patients (marker sensitivity) with keratoconus and in 46% of control group participants. Thus, the specificity of the marker is low (0.54). The odds ratio was 2.4, and the risk ratio was 1.69. Gene expression analysis in the keratoconus patients’ cornea did not reveal an association of the COL5A1 gene expression level with the genotype (p=0.9, Mann-Whitney test). Conclusion. In this study, an association of rs1536482 with keratoconus was identified in a cohort of patients from Russia. However, due to the low specificity of this marker, it cannot be used as a keratoconus classifier. The presence of a marker allele is not associated with the COL5A1 gene expression level.