Identification of Coding Variants in 10q22.1 Associated with Vitiligo in the Chinese Han Population

Area of Science:

• Genetics
• Dermatology
• Human Disease Genetics

Background:

• Vitiligo is a complex autoimmune disorder with a significant genetic component.
• Previous studies have implicated various genetic loci in vitiligo pathogenesis.
• The 10q22.1 region has been suggested to harbor susceptibility genes for vitiligo.

Purpose of the Study:

• To identify causal genetic variants associated with vitiligo in the 10q22.1 chromosomal region.
• To fine-scale analyze the expanded 10q22.1 region for novel vitiligo risk variants.
• To investigate the association of specific single nucleotide polymorphisms (SNPs) in SLC29A3 and CDH23 with vitiligo.

Main Methods:

• Genome-wide association studies (GWAS) dataset analysis with imputation (1117 cases, 1701 controls).
• Fine-scale deep analysis of the 10q22.1 region.
• Genotyping of five coding SNPs in SLC29A3 and CDH23 in an independent Chinese Han population cohort (2479 cases, 2451 controls) using Sequenom MassArray iPLEX1.
• Stepwise conditional analyses to identify independent disease-associated signals.

Main Results:

• A missense SNP in SLC29A3 (rs2252996) showed strong association with vitiligo (p=1.34×10⁻⁸, OR=0.82).
• Three synonymous SNPs in SLC29A3 (rs1084004) and CDH23 (rs12218559, rs10999978) provided suggestive evidence of association (p values ranging from 1.69×10⁻⁶ to 6.90×10⁻⁴).
• Stepwise conditional analyses identified two significant independent disease-associated signals (p<0.05).

Conclusions:

• Four genetic coding variants in SLC29A3 and CDH23 on 10q22.1 are identified as potential contributors to vitiligo susceptibility.
• One missense variant (rs2252996) in SLC29A3 may influence specific disease subphenotypes.
• The findings underscore the significant role of multiple genetic variants in the pathogenesis of vitiligo.