Common ALDH3A1 Gene Variant Associated with Keratoconus Risk in the Polish Population

Mariusz Berdyński; Piotr Krawczyk; Krzysztof Safranow; Beata Borzemska; Jacek P Szaflik; Karolina Nowakowska-Żawrocka; Cezary Żekanowski; Joanna Giebułtowicz

doi:10.3390/jcm11010008

Common ALDH3A1 Gene Variant Associated with Keratoconus Risk in the Polish Population

J Clin Med. 2021 Dec 21;11(1):8. doi: 10.3390/jcm11010008.

Authors

Mariusz Berdyński¹, Piotr Krawczyk², Krzysztof Safranow³, Beata Borzemska¹, Jacek P Szaflik², Karolina Nowakowska-Żawrocka⁴, Cezary Żekanowski¹, Joanna Giebułtowicz⁴

Affiliations

¹ Laboratory of Neurogenetics, Department of Neurodegenerative Disorders, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland.
² Department of Ophthalmology, Medical University of Warsaw, 13 Sierakowskiego Str., 03-709 Warsaw, Poland.
³ Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 72 Powstańców Wlkp. Str., 70-111 Szczecin, Poland.
⁴ Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1 Str., 02-097 Warsaw, Poland.

Abstract

Background: ALDH3A1 protein is important in maintaining corneal physiology and protecting the eye from UV damage. However, none of the genome-wide association studies has indicated that the ALDH3A1 locus is associated with keratoconus. In this study, we examined the potential role of ALDH3A1 variants as risk factors for keratoconus incidence and severity in a large group of Polish keratoconus patients.

Methods: In the first stage we analyzed the coding region sequence of the ALDH3A1 in a subgroup of keratoconus. Then, we genotyped three selected ALDH3A1 variants in a larger KC group of patients (n = 261) and healthy controls (n = 317).

Results: We found that the rs1042183 minor allele A is a risk factor for keratoconus in the dominant model (OR = 2.06, 95%CI = 1.42-2.98, p = 0.00013). The rs2228100 variant genotypes appear to be associated with an earlier age of KC diagnosis in the Polish population (p = 0.055 for comparison of three genotypes and p = 0.022 for the dominant inheritance model).

Conclusions: The rs1042183 variant in ALDH3A1 is associated with keratoconus risk in the Polish population. The differences in the allele frequency between both populations could be partially responsible for the difference in the disease prevalence.

Keywords: aldehyde dehydrogenase; association study genetic; keratoconus (KC); single nucleotide polymorphism (SNP).