The effect of inflammatory cytokines on the risk of hypertrophic scar: a mendelian randomization study.
Humans
Cicatrix, Hypertrophic
/ genetics
Mendelian Randomization Analysis
Genome-Wide Association Study
Leukemia Inhibitory Factor
/ genetics
Osteoprotegerin
/ genetics
Polymorphism, Single Nucleotide
Glial Cell Line-Derived Neurotrophic Factor
/ genetics
Cytokines
/ genetics
Genetic Predisposition to Disease
Risk Factors
Male
Female
Genome-wide association study (GWAS)
Hypertrophic scar
Inflammatory cytokines
Instrumental variable (IV)
Mendelian randomization (MR)
Journal
Archives of dermatological research
ISSN: 1432-069X
Titre abrégé: Arch Dermatol Res
Pays: Germany
ID NLM: 8000462
Informations de publication
Date de publication:
21 Aug 2024
21 Aug 2024
Historique:
received:
13
06
2024
accepted:
05
08
2024
revised:
13
06
2024
medline:
21
8
2024
pubmed:
21
8
2024
entrez:
21
8
2024
Statut:
epublish
Résumé
Hypertrophic scar (HS) results from burns or trauma, causing aesthetic and functional issues. However, observational studies have linked inflammatory cytokines to HS, but the causal pathways involved are unclear. We aimed to determine how circulating inflammatory cytokines contribute to HS formation. Two-sample Mendelian randomization (MR) was used to identify genetic variants associated with hypertrophic scar in a comprehensive, publicly available genome-wide association study (GWAS) involving 766 patients and 207,482 controls of European descent. Additionally, data on 91 plasma proteins were drawn from a GWAS summary involving 14,824 healthy participants. Causal relationships between exposures and outcomes were investigated primarily using the inverse variance weighted (IVW) method. Furthermore, a suite of sensitivity analyses, including MR‒Egger and weighted median approaches, were concurrently employed to fortify the robustness of the conclusive findings. Finally, reverse MR analysis was conducted to evaluate the plausibility of reverse causation between hypertrophic scar and the cytokines identified in our study. In inflammatory cytokines, there was evidence of inverse associations of osteoprotegerin(OPG) levels(OR = 0.59, 95% CI = 0.41 ∼ 0.85, p = 0.01), and leukemia inhibitory factor(LIF) levels(OR = 0.51, 95% CI = 0.32 ∼ 0.82, p = 0.01) are a nominally negative association with hypertrophic scar risk, while CUB domain-domain-containing protein 1(CDCP1) level(OR = 0.59, 95% CI = 0.41 ∼ 0.85, p = 0.01) glial cell line-derived neurotrophic factor(GDNF) levels(OR = 1.42, 95% CI = 1.03 ∼ 1.96, p = 0.01) and programmed cell death 1 ligand 1(PD-L1) levels(OR = 1.47, 95% CI = 1.92 ∼ 2.11, p = 0.04) showed a positive association with hypertrophic scar risk. These associations were similar in the sensitivity analyses. According to our MR findings, OPG and LIF have a protective effect on hypertrophic scar, while CDCP1, GDNF, and PD-L1 have a risk-increasing effect on Hypertrophic scar. Our study adds to the current knowledge on the role of specific inflammatory biomarker pathways in hypertrophic scar. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for hypertrophic scar prevention and treatment.
Identifiants
pubmed: 39167160
doi: 10.1007/s00403-024-03303-7
pii: 10.1007/s00403-024-03303-7
doi:
Substances chimiques
Leukemia Inhibitory Factor
0
Osteoprotegerin
0
LIF protein, human
0
TNFRSF11B protein, human
0
GDNF protein, human
0
Glial Cell Line-Derived Neurotrophic Factor
0
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
551Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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