Corneal ectasias, among which keratoconus (KC) is the single most common entity, are one of the most frequent reasons for corneal grafting in developed countries and a threatening complication of laser in situ keratomileusis. Genome-wide association studies have previously found lysyl oxidase (LOX) and hepatocyte growth factor (HGF) associated with susceptibility to KC development. The aim of our study was to validate the effects of seven single-nucleotide polymorphisms (SNPs) within LOX and HGF over KC. Unrelated Czech cases with KC of European descent (108 males and 57 females, 165 cases in total) and 193 population and gender-matched controls were genotyped using Kompetitive Allele Specific PCR assays. Fisher's exact tests were used to assess the strength of associations. Evidence for association was found for both of the tested loci. It was strongest for rs3735520:G>A near HGF (allelic test odds ratio (OR)=1.45; 95% confidence interval (CI), 1.06-1.98; P=0.018) with A allele being a risk factor and rs2956540:G>C (OR=0.69; 95% CI, 0.50-0.96; P=0.024) within LOX with C allele having a protective effect. This first independent association validation of rs2956540:G>C and rs3735520:G>A suggests that these SNPs may serve as genetic risk markers for KC in individuals of European descent.

• MeSH
• alely MeSH
• běloši MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie * MeSH
• genotyp MeSH
• hepatocytární růstový faktor genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• keratokonus genetika   patologie   MeSH
• lidé MeSH
• rohovka patologie   MeSH
• scavengerové receptory - třída E genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hepatocytární růstový faktor MeSH
• HGF protein, human MeSH Prohlížeč
• OLR1 protein, human MeSH Prohlížeč
• scavengerové receptory - třída E MeSH

PURPOSE: To identify the molecular genetic cause of macular corneal dystrophy (MCD) in four probands, and characterize phenotypic similarities between MCD and keratoconus. METHODS: We performed ophthalmological examination, Scheimpflug imaging (Pentacam, Oculus Inc.), histopathological examination of excised corneal buttons, and direct sequencing of the CHST6 coding region. RESULTS: Pentacam measurements were taken in six eyes of three probands. All showed diffuse corneal thinning with paracentral steepening of the anterior corneal surface that was graded as keratoconus by the integrated software, but without associated ectasia of the posterior corneal surface or regional thinning. Homozygous or compound heterozygous CHST6 mutations were identified in all cases, including two novel mutations, c.13C>T; p.(Arg5Cys) and c.289C>T; p.(Arg97Cys). DISCUSSION: Localized elevation of the anterior corneal curvature can occur in MCD in the absence of other features of keratoconus. The identification of a further two Czech probands with the compound allele c.[484C>G; 599T>G] supports the enrichment of this allele in the study population.

• MeSH
• dědičné dystrofie rohovky genetika   patologie   MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mutace * MeSH
• pachymetrie rohovky MeSH
• rohovka patologie   MeSH
• rohovková topografie MeSH
• sulfotransferasy sacharidů MeSH
• sulfotransferasy genetika   MeSH
• velikost orgánu MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• sulfotransferasy MeSH

Keratoconus (KC) is an eye disease characterized by the progressive thinning and protrusion of the cornea, which results in the loss of visual acuity. This disorder remains poorly understood, although recent studies indicate the involvement of genetic and environmental factors. Recently, we have found that the distribution of the cross-linking enzyme lysyl oxidase (LOX) is markedly decreased in about 63 % of keratoconic specimens. Similarly, LOX activity is significantly reduced by 38 % compared to control tissue. Nearly 70 systemic disorders have been reported in association with KC, most of them affecting the extracellular matrix. In this review we attempted to ascertain whether any KC-associated diseases exhibit signs that may reflect LOX impairment. We hypothesized that very similar changes in the extracellular matrix, particularly at the level of collagen metabolism, including LOX impairment in mitral leaflets, may reflect an association between KC and mitral valve prolapse. Moreover, this putative association is supported by the high frequency of Down syndrome in both diseases. Among other disorders that have been found to coincide with KC, we did not find any in which the LOX enzyme may be directly or indirectly impaired. On the other hand, in cases where KC is present along with other connective tissue disorders (Marfan syndrome, Ehlers-Danlos syndrome and others), KC may not arise as a localized manifestation, but rather may be induced as the result of a more complex connective tissue disorder.

• MeSH
• keratokonus komplikace   enzymologie   MeSH
• lidé MeSH
• lysyloxidasa metabolismus   MeSH
• nemoci pojiva komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• lysyloxidasa MeSH