Dataset Information

Association of 2 Lysyl Oxidase Gene Single Nucleotide Polymorphisms with Keratoconus: A Nationwide Registration Study.

ABSTRACT:

Purpose

Keratoconus (KC) is the most common primary ectatic corneal disease, characterized by progressive thinning of the cornea, affecting its shape and structure and leading to visual loss. Lysyl oxidase is an important component of the extracellular matrix and contributes to the homeostasis of corneal stromal extracellular matrix via enzymatic reaction. This nationwide registration study aims to examine the association of KC with 2 known single nucleotide polymorphisms, rs2956540 and rs10519694, in a population of Iranian descent.

Design

Case-control.

Participants

One hundred seventy-eight subjects with KC and 180 clinically healthy subjects participated in the study.

Methods

Genomic DNA was extracted from peripheral blood samples, and their genotypes were determined using tetra-primer amplification refractory mutation system-polymerase chain reaction.

Main outcome measures

Allele frequency for rs2956540 and rs10519694.

Results

Genotype frequency was significantly different between cases and controls for rs2956540 (P value = 0.019). The rs2956540 C allele carriers were significantly more frequent among KC cases than healthy controls (P value_chi-square = 0.015, P value_{Fisher exact} = 0.017). There was a significant difference in genotype frequency between groups for rs10519694 (P value = 0.001). T allele carriers were significantly more frequent among KC patients (P value_chi-square = 0.002, P value_{Fisher exact} = 0.001). Sex stratification revealed no significant differences in genotype frequency between males and females in cases and controls. Fitting the general linear model showed that rs10519694 could be considered a predictor for the development of KC (P value = 0.001); however, this was not observed for rs2956540 (P value = 0.323).

Conclusions

rs2956540 and rs10519694 are associated with KC in a population of Iranian descent. rs10519694 could potentially be used for KC risk prediction.

SUBMITTER: Niazi S

PROVIDER: S-EPMC9898806 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Association of 2 Lysyl Oxidase Gene Single Nucleotide Polymorphisms with Keratoconus: A Nationwide Registration Study.

Niazi Sana S Moshirfar Majid M Alizadeh Fatemeh F Doroodgar Farideh F Baradaran-Rafii Alireza A Filutowski Oliver O Niazi Feizollah F Ambrósio Renato R

Ophthalmology science 20221109 2

<h4>Purpose</h4>Keratoconus (KC) is the most common primary ectatic corneal disease, characterized by progressive thinning of the cornea, affecting its shape and structure and leading to visual loss. Lysyl oxidase is an important component of the extracellular matrix and contributes to the homeostasis of corneal stromal extracellular matrix via enzymatic reaction. This nationwide registration study aims to examine the association of KC with 2 known single nucleotide polymorphisms, rs2956540 and ...[more]

PMID: 36748061

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Project description:PurposeKeratoconus (KC) is characterized by progressive vision loss due to corneal thinning and structural abnormalities. It is hypothesized that KC is caused by deregulated collagen levels and collagen fibril-maturating enzyme lysyl oxidase (LOX). Further, it is currently not understood whether the gene expression deregulated by the corneal epithelium influences KC pathogenesis. We studied (i) the expressions of the LOX, collagen I (COL IA1), collagen IV (COL IVA1), MMP9, and IL6 genes in KC corneal epithelia, (ii) validated their expression levels in patient tissues, and (iii) correlated expression levels with KC disease severity. The primary goal of this study was to evaluate the importance of these genes in the progression of KC.MethodsWe analyzed the gene expression levels of the key proteins LOX, collagens (COL IA1 and COL IVA1), MMP9, and IL6 in debrided corneal epithelia from a large cohort of KC patients (90 eyes) and compared them to control patients (52 eyes) without KC. We measured the total LOX activity in the tears of KC patients compared to controls. We also correlated the protein expression levels of LOX and collagens by immunohistochemistry (IHC) in primary tissues from KC patients (27 eyes) undergoing keratoplasty compared to healthy donor corneas (15 eyes).ResultsWe observed a significant reduction in LOX transcript levels in KC corneal epithelia, and LOX activity in KC tears correlated with disease severity. Collagen transcripts were also reduced in KC while MMP9 transcript levels were upregulated and correlated with disease severity. IL6 was moderately increased in KC patients. IHC demonstrated a reduction in the protein expression levels of LOX in the epithelium and collagen IV in the basement membrane of KC patients compared to healthy donor corneas.ConclusionsThe data demonstrates that the structural deformity of the KC cornea may be dependent on reduced expressions of collagens and LOX, as well as on MMP9 elevated by the corneal epithelium.

Project description:INTRODUCTION: Migraine is a chronic, neurovascular polygenic disease where genetic and environmental factors are involved in its etiology. Dysfunction of neuronal ion transportation can provide a model for predisposition for common forms of migraine. Mutations in genes encoding ion channels disturb the rhythmic function of exposed tissue that may also explain the episodic nature of migraine. Our aim was to study the single nucleotide polymorphisms of CACNA1A gene in migraine patients. MATERIALS AND METHODS: The subjects were the patients of migraine, in the age range of 18-80 years, diagnosed by a Neurologist, as per the diagnostic criteria of International Headache Society (IHS) Classification 2004 after excluding other causes of headache by clinical examination and relevant investigations. The controls were the age and sex matched healthy persons from the same population excluding the relatives of patients. Only those patients and the controls, who voluntarily participated in the study, were taken and their blood samples were taken for the study. Deoxyribonucleic acid (DNA) extraction was performed according to the manufacturer's protocol for Qiagen DNA extraction kits (Qiagen, Hilden, NRW, Germany). DNA content was quantified by spectrophotometric absorption (Nanodrop Spectrophotometer, BioLab, Scoresby, VIC, Australia). Polymerase chain reaction was performed using an iCycler Thermal Cycler (Bio.Rad, Hercules, CA, USA). The polymorphic analysis of CACNA1A gene was carried out by two methods: Restriction fragment length polymorphism and sequencing. RESULTS: The study included a total of 25 patients of migraine, diagnosed on out-patient department basis as per IHS Classification 2004 and compared with age and sex matched 25 healthy controls. Most of the patients 23 (92%) were below the age of 50 years. 20 of the patients (80%) were females and 5 (20%) were males. The polymorphic analysis of CACNA1A gene revealed the presence of only the wild form of the gene for the codon E993V in both case and control groups. CONCLUSION: In our study, we could not find any polymorphism of CACNA1A gene in the selected patients. Instead the wild type of genotype was found in both patients and controls. This negative result presented here, implies that if the CACNA1A gene is involved in typical migraine (with and without aura), its contribution is very modest and therefore difficult to discern. Nevertheless, there are other genes that could be considered potential candidates for typical migraine susceptibility for which further research is needed.

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Dataset Information

Association of 2 Lysyl Oxidase Gene Single Nucleotide Polymorphisms with Keratoconus: A Nationwide Registration Study.

Purpose

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Publications

Association of 2 Lysyl Oxidase Gene Single Nucleotide Polymorphisms with Keratoconus: A Nationwide Registration Study.

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