Keratoconus is a chronic disorder of the cornea, characterized by its progressive thinning, stretching, and conical protrusion. Diagnostics of subclinical keratoconus, as well as its early stages (forme fruste), is a complex problem. The presence of these forms of keratoconus in a patient is one of the reasons for the development of keratectasia after laser refractive surgery. Currently, the role of genetic factors in keratoconus development has been proven. This indicates the possibility of diagnostics of subclinical and forme fruste keratoconus using genetic markers. Knowledge about the patient's genetic susceptibility to keratoconus would allow correcting the tactics of treatment of refractive anomalies and avoiding serious side effects. The studies of causal mutations indicate the genetic heterogeneity of keratoconus, which complicates the development of a diagnostic panel. Selection of candidate variants from the currently known ones based on clear criteria may be one of the approaches for diagnostic markers search. In this review, we have analyzed articles on keratoconus markers in order to form a list of candidate variants for genotyping in the Russian population. The selection criteria took into account the complexes of symptoms in which a marker was found, populations in which a particular marker was investigated, the presence and results of replication studies. The analysis included markers in VSX1, SOD1, ZEB1, LOX, CAST, DOCK9, TGFBI, HGF, MAP3K19, KCND3, COL4A3, COL4A4, COL5A1, FNDC3B, FOXO1, BANP-ZNF469, MPDZ-NF1B, WNT10A genes. Based on the results of the analysis, the following candidate variants were selected for genotyping in the Russian population of patients with keratoconus: rs1536482 and rs7044529 in the COL5A1 gene, rs5745752 and rs2286194 in the HGF gene, rs4954218 in the MAP3K19 gene, rs4839200 near the KCND3 gene, rs2721051 near the FOXO1 gene, rs1324183 between the MPDZ and the NF1B genes, and rs121908120 in the WNT10A gene.
Keratokonus – éto khronicheskoe zabolevanie rogovitsy, kharakterizuiushcheesia ee progressiruiushchim istoncheniem, ee rastiazheniem i konusovidnym vypiachivaniem. Diagnostika subklinicheskogo keratokonusa, a takzhe ego rannikh stadiĭ (forme fruste) predstavliaet soboĭ slozhnuiu problemu. Nalichie dannykh form keratokonusa u patsienta iavliaetsia odnoĭ iz prichin razvitiia keratéktaziĭ posle lazernykh refraktsionnykh vmeshatel'stv. V nastoiashchee vremia dokazana rol' geneticheskikh faktorov v razvitii keratokonusa. Éto ukazyvaet na vozmozhnost' razrabotki diagnostiki subklinicheskoĭ formy i forme fruste keratokonusa s pomoshch'iu geneticheskikh markerov. Znanie o geneticheskoĭ predraspolozhennosti k keratokonusu u patsienta pozvolilo by skorrektirovat' taktiku lecheniia refraktsionnykh anomaliĭ i izbezhat' tiazhelykh pobochnykh éffektov. Issledovaniia kauzal'nykh mutatsiĭ svidetel'stvuiut o geneticheskoĭ geterogennosti keratokonusa, chto zatrudniaet razrabotku diagnosticheskoĭ paneli. Odnim iz podkhodov k poisku diagnosticheskikh markerov mozhet byt' otbor kandidatnykh variantov iz izvestnykh na dannyĭ moment na osnovanii chetkikh kriteriev. V dannom obzore byli proanalizirovany raboty, posviashchennye izucheniiu markerov keratokonusa, kotorye pozvoliat sformirovat' spisok kandidatnykh variantov dlia genotipirovaniia v rossiĭskoĭ populiatsii. Kriterii otbora uchityvali kompleksy simptomov, pri kotorykh obnaruzhivalsia marker, populiatsii, v kotorykh byl issledovan tot ili inoĭ marker, a takzhe nalichie i rezul'taty replikatsionnykh issledovaniĭ. V analiz byli vkliucheny markery v genakh VSX1, SOD1, ZEB1, LOX, CAST, DOCK9, TGFBI, HGF, MAP3K19, KCND3, COL4A3, COL4A4, COL5A1, FNDC3B, FOXO1, BANP-ZNF469, MPDZ-NF1B, WNT10A. Po rezul'tatam analiza otobrany sleduiushchie kandidatnye varianty dlia genotipirovaniia v rossiĭskoĭ populiatsii patsientov s keratokonusom: rs1536482 i rs7044529 v gene COL5A1, rs5745752 i rs2286194 v gene HGF, rs4954218 v gene MAP3K19, rs4839200 vblizi gena KCND3, rs2721051 vblizi gena FOXO1, rs1324183, raspolozhennyĭ mezhdu genami MPDZ i NF1B, i rs121908120 v gene WNT10A.
Keywords: LOX; SOD1; VSX1; ZEB1; genetic markers; keratoconus.