<i>TNF-α</i> Genetic Predisposition and Higher Expression of Inflammatory Pathway Components in Keratoconus

Arbab, Muneeza; Tahir, Saira; Niazi, Muhammad Khizar; Ishaq, Mazhar; Hussain, Alamdar; Siddique, Pir Muhammad; Saeed, Sadia; Khan, W. A.; Qamar, Raheel; Butt, Azeem Mehmood; Azam, Maleeha

doi:10.1167/iovs.16-21400

Cited by 25 publications

(21 citation statements)

References 38 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the autosomal dominant pattern, there are many phenotypes with incomplete penetrance [ 39 , 123 ]. In other words, there appears to be a genetic predisposition for KC [ 39 , 122 , 124 – 126 ], and the genes associated with KC interact with environmental, genetic, and/or other factors [ 1 , 6 , 24 , 39 , 49 , 67 , 70 , 99 , 109 , 120 , 127 – 129 ]. This underscores the potential role of genetic factors in KC pathogenesis [ 72 , 95 , 125 , 128 , 130 ], which is an important consideration in refractive surgery to treat familial KC [ 130 , 131 ], given the association of KC with other genetic disorders and the imbalance between dizygotic twins [ 59 , 120 , 127 , 130 , 132 ].…”

Section: Heritabilitymentioning

confidence: 99%

Genetic Aspects of Keratoconus: A Literature Review Exploring Potential Genetic Contributions and Possible Genetic Relationships with Comorbidities

Loukovitis¹,

Sfakianakis

Syrmakesi

et al. 2018

Ophthalmol Ther

View full text Add to dashboard Cite

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.

show abstract

Section: Heritabilitymentioning

confidence: 99%

Genetic Aspects of Keratoconus: A Literature Review Exploring Potential Genetic Contributions and Possible Genetic Relationships with Comorbidities

Loukovitis¹,

Sfakianakis

Syrmakesi

et al. 2018

Ophthalmol Ther

View full text Add to dashboard Cite

show abstract

“…The polymorphisms located within the regulatory regions of TNF-α have been reported to influence the expression and secretion of this cytokine 35 . In TNF-α -238 and -308 SNP, the presence of the A-allele increases the binding of transcription factor to the promoter region of TNF-α, thereby altering its expression 36 . Nonetheless, several studies in various infectious diseases have shown the importance of TNF G>A in disease susceptibility, albeit with currently unknown molecular mechanism 37 .…”

Section: Discussionmentioning

confidence: 99%

Detection of Tumor Necrosis Factor- (Tnf- ) Gene Promoters Polymorphism Among Liver Cirrhosis Patients With Chronic Hepatitis B Virus (Hbv) Infection in Surabaya, Indonesia

Wungu

Amin

Ruslan

et al. 2019

IJTID

View full text Add to dashboard Cite

Polymorphisms in TNF-α gene promoter region are known of its role in the production of TNF-α which may influences the pathogenesis of liver disease. SNPs in positions 238 and 308 of TNF-α gene promoters may affect the production of these cytokines. This study was aimed to detect Single Nucleotide Polymorphism (SNP) on -238 and -308 positions in the TNF-α gene promoter among liver cirrhosis patients with HBV infection in Surabaya, Indonesia. This was descriptive exploratory research with cross sectional study design using serum liver cirrhosis patients with HBV infection in Endoscopy Outpatient Clinic Dr. Soetomo General Hospital, Surabaya from April-May 2017. SNPs at -238 and -308 on TNF-α gene promoter (rs361525 and rs1800629 respectively) were detected using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) with primers specific for the TNF-α promoter region and restriction enzymes NcoI and MspI. The genotypes of TNF-α gene promoter were assessed according to the length of the fragments produced in RFLP. Serum TNF-α levels was measured by commercial ELISA. In this study, as much as 149 positive HBsAg patients was found in Endoscopy Outpatient Clinic, Dr. Soetomo General Hospital, Surabaya. From those amount, as much as 30 liver cirrhosis patients with positive HBsAg were obtained. From 2/30 (6.7%) patients showed the GA heterozygote SNP either position -238 or -308. No patient had the AA genotype. Median blood TNF-α level in women (38 ng / L) was higher than in men (33 ng / L). TNF-α levels in patients with GA heterozygote genotype at -238 and -308 in this research was not different than wild-type (GG genotype). Among patients with liver cirrhosis due to chronic HBV infection in Surabaya, Indonesia, Surabaya, we found GA polymorphisms the TNF-α promoter gene at positions -238 and -308 in 6.7% patients, and did not find homozygous AA polymorphisms. Further studies including larger numbers of patients from various ethnic backgrounds in Indonesia are needed to provide robust data on TNF-α gene promoter polymorphisms and their role in the pathogenesis of liver cirrhosis with HBV infection in this country. ABSTRAKPolimorfisme pada promotor gen TNF-α diketahui berperan pada produksi TNF-α yang selanjutnya berperan dalam patogenesis penyakit hepar, penyakit infeksi, serta inflamasi. SNP gen TNF, terutama pada posisi 238 dan 308 dari promotor gen TNF-α telah diidentifikasi dapat memengaruhi produksi sitokin tersebut. Penelitian ini merupakan penelitian pendahuluan yang dilakukan untuk mendeteksi Single Nucleotide Polymorphism (SNP) promotor gen TNF-α posisi -238 dan -308 dari sampel penderita sirosis hati dengan infeksi VHB di Poli Endoskopi RSUD Dr. Soetomo, Surabaya. Jenis penelitian ini adalah penelitian deskriptif eksploratif laboratorik dengan rancangan penelitian cross sectional study yang mengambil sampel pasien penderita sirosis hati dengan infeksi VHB di Poli Endoskopi RSUD Dr. Soetomo Surabaya dari bulan April-Mei 2017. SNP posisi -238 dan -308 (rs361525 dan rs1800629) promotor gen...

show abstract

“…Changes in corneal nerves have been reported in KC, with reduced corneal sensitivity by as much as 21–26% detected in both KC and subclinical KC patients compared to controls [104,105]. Further cellular changes in the KC cornea that have been identified include increased MMP expression and activity (e.g., MMP-1, MMP-2, MMP-9) [106,107,108], elevated expression of pro-inflammatory mediators (e.g., tumor necrosis factor-α, interleukin-6) [109,110,111], and altered ECM-associated pathways (e.g., hydroxyproline, fibronectin, collagen) [112] in KC.…”

Section: Effects Of Dm and Kc On Corneal Structurementioning

confidence: 99%

Mechanisms of Collagen Crosslinking in Diabetes and Keratoconus

McKay

Priyadarsini

Karamichos

2019

Cells

View full text Add to dashboard Cite

Collagen crosslinking provides the mechanical strength required for physiological maintenance of the extracellular matrix in most tissues in the human body, including the cornea. Aging and diabetes mellitus (DM) are processes that are both associated with increased collagen crosslinking that leads to increased corneal rigidity. By contrast, keratoconus (KC) is a corneal thinning disease associated with decreased mechanical stiffness leading to ectasia of the central cornea. Studies have suggested that crosslinking mediated by reactive advanced glycation end products during DM may protect the cornea from KC development. Parallel to this hypothesis, riboflavin-mediated photoreactive corneal crosslinking has been proposed as a therapeutic option to halt the progression of corneal thinning by inducing intra- and intermolecular crosslink formation within the collagen fibrils of the stroma, leading to stabilization of the disease. Here, we review the pathobiology of DM and KC in the context of corneal structure, the epidemiology behind the inverse correlation of DM and KC development, and the chemical mechanisms of lysyl oxidase-mediated crosslinking, advanced glycation end product-mediated crosslinking, and photoreactive riboflavin-mediated corneal crosslinking. The goal of this review is to define the biological and chemical pathways important in physiological and pathological processes related to collagen crosslinking in DM and KC.

show abstract

TNF-α Genetic Predisposition and Higher Expression of Inflammatory Pathway Components in Keratoconus

Cited by 25 publications

References 38 publications

Genetic Aspects of Keratoconus: A Literature Review Exploring Potential Genetic Contributions and Possible Genetic Relationships with Comorbidities

Genetic Aspects of Keratoconus: A Literature Review Exploring Potential Genetic Contributions and Possible Genetic Relationships with Comorbidities

Detection of Tumor Necrosis Factor- (Tnf- ) Gene Promoters Polymorphism Among Liver Cirrhosis Patients With Chronic Hepatitis B Virus (Hbv) Infection in Surabaya, Indonesia

Mechanisms of Collagen Crosslinking in Diabetes and Keratoconus

Contact Info

Product

Resources

About