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The Proteins of Keratoconus: a Literature Review Exploring Their Contribution to the Pathophysiology of the Disease.

ABSTRACT: INTRODUCTION:Keratoconus (KC) is a complex, genetically heterogeneous multifactorial degenerative disorder characterized by corneal ectasia and thinning. Its incidence is approximately 1/2000-1/50,000 in the general population. KC is associated with moderate to high myopia and irregular astigmatism, resulting in severe visual impairment. KC structural abnormalities primarily relate to the weakening of the corneal collagen. Their understanding is crucial and could contribute to effective management of the disease, such as with the aid of corneal cross-linking (CXL). The present article critically reviews the proteins involved in the pathophysiology of KC, with particular emphasis on the characteristics of collagen that pertain to CXL. METHODS:PubMed, MEDLINE, Google Scholar and GeneCards databases were screened for relevant articles published in English between January 2006 and June 2018. Keyword combinations of the words "keratoconus," "risk factor(s)," "genetics," "genes," "genetic association(s)," "proteins", "collagen" and "cornea'' were used. In total, 272 articles were retrieved, reviewed and selected, with greater weight placed on more recently published evidence. Based on the reviewed literature, an attempt was made to tabulate the up- and down-regulation of genes involved in KC and their protein products and to delineate the mechanisms involved in CXL. RESULTS:A total of 117 proteins and protein classes have been implicated in the pathogenesis and pathophysiology of KC. These have been tabulated in seven distinct tables according to their gene coding, their biochemistry and their metabolic control. CONCLUSION:The pathogenesis and pathophysiology of KC remain enigmatic. Emerging evidence has improved our understanding of the molecular characteristics of KC and could further improve the success rate of CXL therapies.

SUBMITTER: Loukovitis E

PROVIDER: S-EPMC6822850 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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The Proteins of Keratoconus: a Literature Review Exploring Their Contribution to the Pathophysiology of the Disease.

Loukovitis Eleftherios E Kozeis Nikolaos N Gatzioufas Zisis Z Kozei Athina A Tsotridou Eleni E Stoila Maria M Koronis Spyros S Sfakianakis Konstantinos K Tranos Paris P Balidis Miltiadis M Zachariadis Zacharias Z Mikropoulos Dimitrios G DG Anogeianakis George G Katsanos Andreas A Konstas Anastasios G AG

Advances in therapy 20190730 9

<h4>Introduction</h4>Keratoconus (KC) is a complex, genetically heterogeneous multifactorial degenerative disorder characterized by corneal ectasia and thinning. Its incidence is approximately 1/2000-1/50,000 in the general population. KC is associated with moderate to high myopia and irregular astigmatism, resulting in severe visual impairment. KC structural abnormalities primarily relate to the weakening of the corneal collagen. Their understanding is crucial and could contribute to effective ...[more]

PMID: 31363996

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Project description:IntroductionKeratoconus (KC) is a complex, genetically heterogeneous, multifactorial degenerative disorder that is accompanied by corneal ectasia which usually progresses asymmetrically. With an incidence of approximately 1 per 2000 and 2 cases per 100,000 population presenting annually, KC follows an autosomal recessive or dominant pattern of inheritance and is, apparently, associated with genes that interact with environmental, genetic, and/or other factors. This is an important consideration in refractive surgery in the case of familial KC, given the association of KC with other genetic disorders and the imbalance between dizygotic twins. The present review attempts to identify the genetic loci contributing to the different KC clinical presentations and relate them to the common genetically determined comorbidities associated with KC.MethodsThe PubMed, MEDLINE, Google Scholar, and GeneCards databases were screened for KC-related articles published in English between January 2006 and November 2017. Keyword combinations of "keratoconus," "risk factor(s)," "genetics," "genes," "genetic association(s)," and "cornea" were used. In total, 217 articles were retrieved and analyzed, with greater weight placed on the more recent literature. Further bibliographic research based on the 217 articles revealed another 124 relevant articles that were included in this review. Using the reviewed literature, an attempt was made to correlate genes and genetic risk factors with KC characteristics and genetically related comorbidities associated with KC based on genome-wide association studies, family-based linkage analysis, and candidate-gene approaches.ResultsAn association matrix between known KC-related genes and KC symptoms and/or clinical signs together with an association matrix between identified KC genes and genetically related KC comorbidities/syndromes were constructed.ConclusionTwenty-four genes were identified as potential contributors to KC and 49 KC-related comorbidities/syndromes were found. More than 85% of the known KC-related genes are involved in glaucoma, Down syndrome, connective tissue disorders, endothelial dystrophy, posterior polymorphous corneal dystrophy, and cataract.

Project description:Objective: Spondyloarthritis (SpA) are a group of diseases with a high heritability, whose pathogenesis is strongly determined by an interplay between genetic and environmental factor. Therefore, the aim of our study was to determine whether genetic variants could also influence response to therapy in SpA. Methods: A systematic literature review (SLR) was conducted in PubMed and Web of Science core collection, without publication-year restrictions (Last search 8th April 2021). The search strategy was formulated according to the PEO format (Population, Exposure, Outcome) for observational studies. The population was adult (≥18 years) patients with SpA. The exposure was inheritable genetic variations of any gene involved in the disease pathogenesis/drug metabolism. The outcome was response to the drug, both as dichotomous (response yes/no) and as continuous outcomes. Exclusion criteria were: (1) languages other than English, (2) case series, case reports, editorials, and reviews, (3) studies reporting genetic contribution to drug response only limited to extra-musculoskeletal features of SpA, (4) epigenetic modifications. Quality of the included study was independently assessed by two authors. Results: After deduplication, 393 references were screened by two authors, which led to the final inclusion of 26 articles, pertinent with the research question, that were considered for qualitative synthesis. Among these, 10 cohort, one cross-sectional, and five case-control studies were considered of at least good quality according to Newcastle-Ottawa Scale (NOS). In studies about TNF-blockers therapy: (1) polymorphisms of the TNF receptor superfamily 1A/1B (TNFRSF1A/1B) genes were most frequently able to predict response, (2) -238 and -308 polymorphisms of TNFα gene were studied with conflicting results, (3) TNFα polymorphism rs1799724, rs1799964, -857, -1,013, +489 predicted drug response in non-adjusted analysis, (4) PDE3A rs3794271 had a linear relationship with DAS28 reduction after anti-TNFα therapy. DHFR polymorphism +35,289 was able to predict response to methotrexate. Conclusions: Our SLR highlighted the existence of a genetic component in determining drug response. However, further studies are warranted to better define quantify it.

Dataset Information

The Proteins of Keratoconus: a Literature Review Exploring Their Contribution to the Pathophysiology of the Disease.

Publications

The Proteins of Keratoconus: a Literature Review Exploring Their Contribution to the Pathophysiology of the Disease.

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