IRF5 Variants Are Risk Factors for Systemic Lupus Erythematosus in Two Mexican Populations

Area of Science:

• Genetics
• Immunology
• Rheumatology

Background:

• Interferon regulatory factor 5 (IRF5) is a key gene in systemic lupus erythematosus (SLE) susceptibility across diverse ethnicities.
• Previous research linked specific IRF5 single-nucleotide variants (SNVs) to SLE in Mexico City, but the Yucatan population remains understudied.
• The Yucatan population has a distinct Amerindian genetic component, necessitating further investigation into IRF5's role.

Purpose of the Study:

• To replicate the association between IRF5 variants and SLE susceptibility in Central Mexico and Yucatan.
• To investigate the novel IRF5 SNV rs59110799G/T in SLE patients.
• To explore potential functional implications of identified IRF5 variants.

Main Methods:

• Genotyping of 204 SLE patients and 160 controls from Central Mexico, and 184 SLE patients and 184 controls from Yucatan.
• Analysis of IRF5 SNVs rs2004640G/T, rs2070197T/C, rs10954213G/A, and rs59110799G/T using TaqMan assays.
• In silico prediction of functional consequences for IRF5 variants using web tools.

Main Results:

• In Central Mexico, significant associations were found for rs2070197C (OR 2.08), rs10954213A (OR 1.59), and rs59110799G (OR 1.71) with SLE.
• In Yucatan, significant associations included rs2004640T (OR 1.51), rs2070197C (OR 1.62), rs10954213A (OR 1.67), and rs59110799G (OR 1.44).
• Allele rs2070197C and rs10954213A showed consistent associations in both populations.

Conclusions:

• Genetic variations in IRF5 contribute to SLE susceptibility in both Central Mexico and Yucatan.
• The study underscores population-specific genetic differences in SLE.
• IRF5 is confirmed as a significant risk factor for SLE in these distinct Mexican populations.