Joint study of the associations of HLA-B and the transmembrane short tandem repeat polymorphism of MICA protein with alopecia areata shows independent associations of both with the disease

Clin Exp Dermatol. 2020 Aug;45(6):699-704. doi: 10.1111/ced.14208. Epub 2020 Jun 10.

Abstract

Background: Alopecia areata (AA) is a skin disease that produces hair loss in patches of skin. The underlying mechanism of AA is a loss of immune privilege of hair follicles, which are then attacked by natural killer (NK) cells. A previous genome-wide association study linked single nucleotide polymorphisms of the protein MHC class I chain-related A (MICA) to this disease. MICA is the ligand for the activating receptor NKG2D, expressed mainly by NK cells and CD8+ cytotoxic T cells. As the aforementioned study did not include short tandem repeats (STRs) of MICA, we decided to study these in relation to AA.

Aim: To study the association of STRs with AA, alongside that of human leucocyte antigen (HLA) locus B, which is closely linked to MICA.

Methods: DNA amplicon size analysis was carried out, and HLA-B locus genomic typing was performed by PCR-sequence-specific oligonucleotide analysis.

Results: We observed an association between AA and both MICA*009 and HLA-B14; associations were also observed between HLA-B alleles and MICA alleles, which have both been previously found to be connected with AA, but never studied together.

Conclusions: We conclude that it is important to study HLA-B and MICA together to avoid the influence of their association in experiments in which they are investigated separately.

MeSH terms

  • Alopecia Areata / genetics*
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-B Antigens / genetics
  • HLA-B14 Antigen / genetics*
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Microsatellite Repeats*
  • Polymorphism, Single Nucleotide
  • Sequence Analysis, DNA

Substances

  • HLA-B Antigens
  • HLA-B14 Antigen
  • Histocompatibility Antigens Class I
  • MHC class I-related chain A