Research output: Contribution to journal › Article › peer-review
Rare single nucleotide variants in COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482. / Skorodumova, Liubov O.; Belodedova, Alexandra V.; Sharova, Elena I.; Zakharova, Elena S.; Iulmetova, Liliia N.; Bikbov, Mukharram M.; Usubov, Emin L.; Antonova, Olga P.; Selezneva, Oksana V.; Levchenko, Anastasia; Fedorenko, Olga Yu; Ivanova, Svetlana A.; Gainetdinov, Raul R.; Malyugin, Boris E.
In: BMC Ophthalmology, Vol. 21, No. 1, 357, 12.2021.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Rare single nucleotide variants in COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482
AU - Skorodumova, Liubov O.
AU - Belodedova, Alexandra V.
AU - Sharova, Elena I.
AU - Zakharova, Elena S.
AU - Iulmetova, Liliia N.
AU - Bikbov, Mukharram M.
AU - Usubov, Emin L.
AU - Antonova, Olga P.
AU - Selezneva, Oksana V.
AU - Levchenko, Anastasia
AU - Fedorenko, Olga Yu
AU - Ivanova, Svetlana A.
AU - Gainetdinov, Raul R.
AU - Malyugin, Boris E.
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: Keratoconus is a chronic degenerative disorder of the cornea characterized by thinning and cone-shaped protrusions. Although genetic factors play a key role in keratoconus development, the etiology is still under investigation. The occurrence of single-nucleotide polymorphisms (SNPs) associated with keratoconus in Russian patients is poorly studied. The purpose of this study was to validate whether three reported keratoconus-associated SNPs (rs1536482 near the COL5A1 gene, rs2721051 near the FOXO1 gene, rs1324183 near the MPDZ gene) are also actual for a Russian cohort of patients. Additionally, we investigated the COL5A1 promoter sequence for single-nucleotide variants (SNVs) in a subgroup of keratoconus patients with at least one rs1536482 minor allele (rs1536482+) to assess the role of these SNVs in keratoconus susceptibility associated with rs1536482. Methods: This case-control study included 150 keratoconus patients and two control groups (main and additional, 205 and 474 participants, respectively). We performed PCR targeting regions flanking SNVs and the COL5A1 promoter, followed by Sanger sequencing of amplicons. The additional control group was genotyped using an SNP array. Results: The minor allele frequency was significantly different between the keratoconus and control cohorts (main and combined) for rs1536482, rs2721051, and rs1324183 (p-value < 0.05). The rare variants rs1043208782 and rs569248712 were found in the COL5A1 promoter in two out of 94 rs1536482+ keratoconus patients. Conclusion: rs1536482, rs2721051, and rs1324183 were associated with keratoconus in a Russian cohort. SNVs in the COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482.
AB - Background: Keratoconus is a chronic degenerative disorder of the cornea characterized by thinning and cone-shaped protrusions. Although genetic factors play a key role in keratoconus development, the etiology is still under investigation. The occurrence of single-nucleotide polymorphisms (SNPs) associated with keratoconus in Russian patients is poorly studied. The purpose of this study was to validate whether three reported keratoconus-associated SNPs (rs1536482 near the COL5A1 gene, rs2721051 near the FOXO1 gene, rs1324183 near the MPDZ gene) are also actual for a Russian cohort of patients. Additionally, we investigated the COL5A1 promoter sequence for single-nucleotide variants (SNVs) in a subgroup of keratoconus patients with at least one rs1536482 minor allele (rs1536482+) to assess the role of these SNVs in keratoconus susceptibility associated with rs1536482. Methods: This case-control study included 150 keratoconus patients and two control groups (main and additional, 205 and 474 participants, respectively). We performed PCR targeting regions flanking SNVs and the COL5A1 promoter, followed by Sanger sequencing of amplicons. The additional control group was genotyped using an SNP array. Results: The minor allele frequency was significantly different between the keratoconus and control cohorts (main and combined) for rs1536482, rs2721051, and rs1324183 (p-value < 0.05). The rare variants rs1043208782 and rs569248712 were found in the COL5A1 promoter in two out of 94 rs1536482+ keratoconus patients. Conclusion: rs1536482, rs2721051, and rs1324183 were associated with keratoconus in a Russian cohort. SNVs in the COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482.
KW - COL5A1
KW - Cornea
KW - FOXO1
KW - Genotyping
KW - GWAS
KW - Keratoconus
KW - MPDZ
KW - Promoter
KW - SNP
KW - Promoter Regions, Genetic
KW - Genetic Predisposition to Disease
KW - Humans
KW - Case-Control Studies
KW - Collagen Type V/genetics
KW - Keratoconus/genetics
KW - Polymorphism, Single Nucleotide
KW - CENTRAL CORNEAL THICKNESS
KW - GENOME-WIDE ASSOCIATION
UR - http://www.scopus.com/inward/record.url?scp=85116827700&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/81c2667d-72d6-372f-bf7e-a62e7b1b05c5/
U2 - 10.1186/s12886-021-02128-6
DO - 10.1186/s12886-021-02128-6
M3 - Article
C2 - 34625056
AN - SCOPUS:85116827700
VL - 21
JO - BMC Ophthalmology
JF - BMC Ophthalmology
SN - 1471-2415
IS - 1
M1 - 357
ER -
ID: 87872105