Association of<i>Lysyl oxidase (LOX)</i>Polymorphisms with the Risk of Keratoconus in an Iranian Population

Hasanian-Langroudi, Farzaneh; Saravani, Ramin; Validad, Mohammad-Hosein; Bahari, Gholamreza; Yari, Davood

doi:10.3109/13816810.2014.881507

Cited by 38 publications

(41 citation statements)

References 36 publications

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“…8 The main statistics used here (allelic test) implicitly assume codominance, and is similar to the additive models assumed in the previous reports. 8,9,13,15 Although some caution is invited in the interpretation of our findings because of the relatively small sample size, the validation of rs2956540:G4C and rs3735520:G4A showing the same effect directions as previous studies in populations of European ancestry adds weight to the existing evidence. 8,9 Although not reaching a statistically significant threshold, the higher MAF of rs1800449:C4T and rs10519694:C4T in controls compared with the KC cases in our study, was consistent with protective effects of these alleles reported in another study using Caucasian case-control panels (Supplementary Table 2).…”

Section: Discussionmentioning

confidence: 47%

Validation of rs2956540:G>C and rs3735520:G>A association with keratoconus in a population of European descent

et al. 2015

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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:G4A 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:G4C (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:G4C and rs3735520:G4A suggests that these SNPs may serve as genetic risk markers for KC in individuals of European descent.

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Section: Discussionmentioning

confidence: 47%

Validation of rs2956540:G>C and rs3735520:G>A association with keratoconus in a population of European descent

et al. 2015

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“…1) 21–24, 32, 37–54 . Among these 24 studies, 20 were candidate gene studies conducted in different populations, including Whites 39, 41, 43, 44, 47, 49–52, 55 , Arabic 37, 38, 40 , Chinese 45, 56 , Korean 53, 54 , Japanese 48 , Indian 46 , and Turkish 42 . The total sample sizes from these candidate gene studies were 3,037 patients with keratoconus and 9,928 controls.…”

Section: Resultsmentioning

confidence: 99%

Genetic associations for keratoconus: a systematic review and meta-analysis

Rong

et al. 2017

Sci Rep

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Genetic associations for keratoconus could be useful for understanding disease pathogenesis and discovering biomarkers for early detection of the disease. We conducted a systematic review and meta-analysis to summarize all reported genetic associations for the disease. We searched in the MEDLINE, Embase, Web of Science, and HuGENET databases for genetic studies of keratoconus published from 1950 to June 2016. The summary odds ratio and 95% confidence intervals of all polymorphisms were estimated using the random-effect model. Among 639 reports that were retrieved, 24 fulfilled required criteria as eligible studies for meta-analysis, involving a total of 53 polymorphisms in 28 genes/loci. Results of our meta-analysis lead to the prioritization of 8 single-nucleotide polymorphisms (SNPs) in 6 genes/loci for keratoconus in Whites. Of them 5 genes/loci were originally detected in genome-wide association studies, including FOXO1 (rs2721051, P = 5.6 × 10−11), RXRA-COL5A1 (rs1536482, P = 2.5 × 10−9), FNDC3B (rs4894535, P = 1.4 × 10−8), IMMP2L (rs757219, P = 6.1 × 10−7; rs214884, P = 2.3 × 10−5), and BANP-ZNF469 (rs9938149, P = 1.3 × 10−5). The gene COL4A4 (rs2229813, P = 1.3 × 10−12; rs2228557, P = 4.5 × 10−7) was identified in previous candidate gene studies. We also found SNPs in 10 genes/loci that had a summary P value < 0.05. Sensitivity analysis indicated that the results were robust. Replication studies and understanding the roles of these genes in keratoconus are warranted.

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“…136 Polymorphisms of the LOX coding gene are correlated with an increased likelihood to develop keratoconus. 137,138 In 63% of cases of keratoconus, LOX distribution has been found to be markedly decreased and its activity to be more than 2.5 times lower than that of control cases. 139,140 A study in Russia has shown that the increase in pH of the tears causes biochemical changes in the periphery of the cornea that prevent the passage of Keratoconus IL-1α, interleukin 1α; KC, keratoconous; β-NGF, nerve growth factor-β; PDGF, platelet-derived growth factor; PGE2, prostaglandin E2; PIGR, polymeric immunoglobulin receptor; RGP, rigid gas permeable; TGF-β1, transforming growth factor β1;…”

Section: Enzymatic Imbalancementioning

confidence: 99%

Keratoconus: an inflammatory disorder?

Galvis

Sherwin

Tello

et al. 2015

Eye

303

199

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Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.

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Association ofLysyl oxidase (LOX)Polymorphisms with the Risk of Keratoconus in an Iranian Population

Abstract: Our study demonstrated that the LOX rs1800449 genotypes (AA and GA + AA) and allele (A) appears to confer risk for susceptibility to keratoconus.

Cited by 38 publications

References 36 publications

Validation of rs2956540:G>C and rs3735520:G>A association with keratoconus in a population of European descent

Validation of rs2956540:G>C and rs3735520:G>A association with keratoconus in a population of European descent

Genetic associations for keratoconus: a systematic review and meta-analysis

Keratoconus: an inflammatory disorder?

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