Toll-like-Receptor Gene Polymorphisms in Tunisian Endemic Pemphigus Foliaceus

Area of Science:

• Immunogenetics
• Dermatology
• Autoimmune Diseases

Background:

• Pemphigus foliaceus (PF) is an autoimmune blistering disease.
• Genetic susceptibility and environmental factors are implicated in PF pathogenesis.
• Toll-like receptors (TLRs) play a role in immune responses and have been linked to autoimmune diseases.

Purpose of the Study:

• To investigate the association between polymorphisms in Toll-like receptor 2 (TLR2), TLR3, TLR4, and TLR7 genes and Pemphigus foliaceus (PF) in a Tunisian population.
• To analyze the influence of epidemiological features on these genetic associations.

Main Methods:

• Genotyping of 14 polymorphisms across TLR2, TLR3, TLR4, and TLR7 genes in 93 Tunisian PF patients and 193 healthy controls.
• Stratification analysis based on epidemiological features (endemic vs. sporadic, age of onset).
• Statistical analysis including Odds Ratio (OR) and P-values to determine genetic associations.

Main Results:

• No overall association found in the entire cohort.
• Specific TLR2 GT repeat polymorphisms (GT18 allele, GT18/GT19 genotype) were associated with increased risk in endemic PF.
• Medium TLR2 GT repeats showed higher frequency in patients, suggesting a risk factor.
• TLR3-rs574305 AA genotype and A allele were linked to PF onset over 35 years.
• TLR4 rs3775294 A allele demonstrated a protective effect in sporadic PF.
• No significant associations were found for TLR4 and TLR7 polymorphisms.

Conclusions:

• TLR2 and TLR3 gene polymorphisms are significantly associated with increased susceptibility to Pemphigus foliaceus in the Tunisian population.
• Specific polymorphisms within TLR2 and TLR3 may influence disease risk based on epidemiological factors.
• Further research is needed to elucidate the precise mechanisms linking these TLR polymorphisms to PF pathogenesis.