Genetic polymorphisms and their association with atopic dermatitis in skin of color – A comprehensive review

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial etiology, including genetic, environmental, and immunological components. The disease disproportionately affects children and contributes significantly to the global disease burden, especially in high-income countries. While several genetic factors have been established in European populations, limited research exists on the genetic landscape of AD in individuals with skin of color (SOC), which includes Asian, African, Latin, Pacific Islander, and Indigenous populations. SOC is under-represented in dermatologic research, contributing to diagnostic, therapeutic, and epidemiologic gaps. Genetic heterogeneity and pigment-related diagnostic challenges complicate the clinical management of AD in these groups. This review aims to summarize current knowledge on genetic polymorphisms associated with AD; highlight differences in genetic susceptibility and mutation profiles in SOC populations, particularly in Indian patients; discuss clinical implications of identified polymorphisms for disease onset, severity, and treatment response; identify limitations in existing research; and propose future directions for inclusive genetic studies. Filaggrin (FLG) mutations, particularly loss-of-function variants, play a crucial role in AD susceptibility. Indian studies reveal novel FLG mutations not previously identified in other populations, with significant association with early disease onset and high Immunoglobulin E (IgE) levels. Other single-nucleotide polymorphisms in immune and barrier genes (e.g., Interleukin-4 [IL-4], IL-13, serine protease inhibitor Kazal type 5, toll-like receptor 2) further contribute to ethnic-specific risk profiles. SOC populations show lower prevalence of common European FLG mutations but unique mutations with distinct clinical outcomes. Understanding the genetic architecture of AD in SOC is critical for early diagnosis, risk stratification, and personalized therapy. Future directions include inclusive multi-omics research, creation of biobanks, and better ethnic representation in genomic databases.