Unveiling the TGF- β1 paradox : Significant implication of TGF- β1 promoter variants and its mRNA and protein expression in atopic dermatitis
Copyright © 2023 Elsevier Ltd. All rights reserved..
BACKGROUND: Atopic Dermatitis (AD) is a chronic inflammatory skin disorder with evidence of lichenification in later stages. There is mounting evidence supporting the role of TGF- β1 in mediating inflammation as well as subsequent tissue remodeling, often resulting in fibrosis. Given the role of genetic variants in the differential expression of TGF-β1 in various diseases, this study seeks to ascertain the role of TGF-β1 promoter variants (rs1800469 and rs1800468) in AD susceptibility, as well as their association with TGF- β1 mRNA expression, TGF- β1 serum levels and skin prick test positivity in Atopic Dermatitis patients.
METHODS: An aggregate of 246 subjects including 134 AD cases and 112 matched healthy controls were genotyped for TGF-β1 promoter polymorphisms by PCR-RFLP. TGF- β1 mRNA was quantified by quantitative Real-Time PCR (qRT-PCR), Vitamin-D levels by chemiluminescence, and serum TGF- β1, and total IgE levels were determined by ELISA. In-vivo allergy testing was performed for the evaluation of allergic reactions to house dust mites and food allergens.
RESULTS: A higher frequency of TT genotypes of rs1800469 (OR = 7.7, p = 0.0001) and GA+AA genotypes of rs1800468 (OR-4.4, p < 0.0001) were observed in AD cases than those in controls. Haplotype analysis demonstrated that TG haplotype carriers had an increased risk of AD (p = 0.013). Quantitative analysis revealed a significant upregulation of both mRNA (p = 0.0002) and serum levels (p < 0.0001) of TGF- β1 with a substantial positive correlation between them (Correlation coefficient=0.504; p = 0.01). Moreover, serum TGF-β1 levels were associated with quality of life (p = 0.03), the severity of the disease (p = 0.03), and House dust mite allergy (p = 0.01) whereas TGF-β1 mRNA levels positively correlated with disease severity(p = 0.02). Stratification analysis revealed that the TT genotype of rs1800469 was associated with higher IgE levels (p = 0.01) and eosinophil percentage(p = 0.007) whereas the AA genotype of rs1800468 correlated with elevated serum IgE levels (p = 0.01). Besides, no significant association of genotypes with mRNA and serum expression of TGF-β1 was observed.
CONCLUSION: Our study indicates that TGF-β1 promoter SNPs bear a significant risk of AD development. Moreover, upregulation of TGF-β1 mRNA and serum levels and their association with disease severity, quality of life, and HDM allergy suggests its role as a diagnostic/prognostic biomarker that could help in the development of new therapeutic and prevention strategies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:157 |
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| Enthalten in: |
Molecular immunology - 157(2023) vom: 15. Mai, Seite 214-224 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shafi, Tabasum [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.05.2023 Date Revised 09.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.molimm.2023.04.006 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Shafi, Tabasum |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Unveiling the TGF- β1 paradox |b Significant implication of TGF- β1 promoter variants and its mRNA and protein expression in atopic dermatitis |
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| 500 | |a Date Revised 09.05.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier Ltd. All rights reserved. | ||
| 520 | |a BACKGROUND: Atopic Dermatitis (AD) is a chronic inflammatory skin disorder with evidence of lichenification in later stages. There is mounting evidence supporting the role of TGF- β1 in mediating inflammation as well as subsequent tissue remodeling, often resulting in fibrosis. Given the role of genetic variants in the differential expression of TGF-β1 in various diseases, this study seeks to ascertain the role of TGF-β1 promoter variants (rs1800469 and rs1800468) in AD susceptibility, as well as their association with TGF- β1 mRNA expression, TGF- β1 serum levels and skin prick test positivity in Atopic Dermatitis patients | ||
| 520 | |a METHODS: An aggregate of 246 subjects including 134 AD cases and 112 matched healthy controls were genotyped for TGF-β1 promoter polymorphisms by PCR-RFLP. TGF- β1 mRNA was quantified by quantitative Real-Time PCR (qRT-PCR), Vitamin-D levels by chemiluminescence, and serum TGF- β1, and total IgE levels were determined by ELISA. In-vivo allergy testing was performed for the evaluation of allergic reactions to house dust mites and food allergens | ||
| 520 | |a RESULTS: A higher frequency of TT genotypes of rs1800469 (OR = 7.7, p = 0.0001) and GA+AA genotypes of rs1800468 (OR-4.4, p < 0.0001) were observed in AD cases than those in controls. Haplotype analysis demonstrated that TG haplotype carriers had an increased risk of AD (p = 0.013). Quantitative analysis revealed a significant upregulation of both mRNA (p = 0.0002) and serum levels (p < 0.0001) of TGF- β1 with a substantial positive correlation between them (Correlation coefficient=0.504; p = 0.01). Moreover, serum TGF-β1 levels were associated with quality of life (p = 0.03), the severity of the disease (p = 0.03), and House dust mite allergy (p = 0.01) whereas TGF-β1 mRNA levels positively correlated with disease severity(p = 0.02). Stratification analysis revealed that the TT genotype of rs1800469 was associated with higher IgE levels (p = 0.01) and eosinophil percentage(p = 0.007) whereas the AA genotype of rs1800468 correlated with elevated serum IgE levels (p = 0.01). Besides, no significant association of genotypes with mRNA and serum expression of TGF-β1 was observed | ||
| 520 | |a CONCLUSION: Our study indicates that TGF-β1 promoter SNPs bear a significant risk of AD development. Moreover, upregulation of TGF-β1 mRNA and serum levels and their association with disease severity, quality of life, and HDM allergy suggests its role as a diagnostic/prognostic biomarker that could help in the development of new therapeutic and prevention strategies | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a PCR-RFLP | |
| 650 | 4 | |a Serum IgE levels | |
| 650 | 4 | |a Skin prick test | |
| 650 | 4 | |a TGF-β1 polymorphism | |
| 650 | 4 | |a TGF-β1 serum levels | |
| 650 | 4 | |a mRNA expression | |
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| 700 | 1 | |a Bashir, Sheikh Adil |e verfasserin |4 aut | |
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