Expressive

rs117222852 (HLA-DRB1): Allergen Sensitization GWAS

Key takeaways

  • rs117222852 sits in the HLA class II immune gene region, encoding proteins that present allergen fragments to T-helper cells and shape IgE responses.
  • A GWAS of 564 Japanese children found genome-wide significant associations with grass pollen (Phl p 1) and profilin sensitization.
  • Evidence is preliminary: small sample (n=564), single pediatric Japanese cohort, and no independent replication reported.
  • GTEx data link the alternate allele to increased expression of nearby HLA genes in heart, breast, adipose, and thyroid tissue.

Key takeaways

  • rs117222852 sits within the HLA class II immune gene region, encoding proteins that present allergen fragments to T-helper cells and shape IgE antibody responses.
  • A genome-wide association study of 564 Japanese children found genome-wide significant associations between this region and sensitization to grass pollen (Phl p 1) and profilin, a cross-reactive plant pan-allergen.
  • Evidence is preliminary: small sample (n=564), single pediatric Japanese cohort, and no independent replication reported.
  • GTEx data link the alternate allele to increased expression of nearby HLA genes in heart, breast, adipose, and thyroid tissue.

What the research says

A genome-wide association study (GWAS) - the first ever conducted specifically for allergen component sensitization - enrolled 564 children from the Tokyo Children's Health, Illness, and Development (T-CHILD) cohort and measured allergen component-specific IgE at age 9 using allergen microarray immunoassays. The HLA class II region (HLA-DRB1 / HLA-DQA1), where rs117222852 resides, reached genome-wide significance (P < 5.0 × 10^-8) for two distinct allergen sensitizations: Phl p 1, the major allergen component of Timothy grass pollen, and profilin, a structural pan-allergen found across diverse plant sources. The authors note this signal is consistent with the known immunological role of HLA class II genes in presenting peptide antigens to adaptive immune cells and shaping IgE-mediated responses.

Reported associations

  • Timothy grass pollen sensitization (Phl p 1): Genome-wide significant association (P < 5.0 × 10^-8) between the HLA class II locus and sensitization to Phl p 1 at age 9 in 564 Japanese children.
  • Profilin sensitization: Genome-wide significant association (P < 5.0 × 10^-8) between the same locus and sensitization to profilin, a pan-allergen cross-reactive across pollens, fruits, and vegetables.

Evidence quality

The sole source study enrolled 564 participants from a single Japanese pediatric cohort; this is a small sample by GWAS standards and limits statistical power to detect modest effects. Both allergen associations cleared the conventional genome-wide significance threshold (P < 5.0 × 10^-8). The authors describe these as the first GWAS findings for allergen component-level phenotypes, and no independent replication cohort was reported. The study population - Japanese children at age 9 - limits generalizability to other ancestries, adult populations, and clinical allergy outcomes. The evidence should be considered preliminary.

Tissue-specific expression effects

  • HLA-DRB6: The alternate allele is associated with increased expression of HLA-DRB6 in esophageal gastroesophageal junction, heart atrial appendage, breast mammary tissue, subcutaneous adipose tissue, visceral (omental) adipose tissue, and thyroid GTEx Portal.
  • HLA-DQA2: The alternate allele is associated with increased expression of HLA-DQA2 in breast mammary tissue and esophageal gastroesophageal junction GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs117222852 associated with?

rs117222852 is located in the HLA class II immune gene region and has been linked to allergen sensitization - specifically to grass pollen (Phl p 1) and profilin - in a genome-wide association study of 564 Japanese children.

What do HLA-DRB1 and HLA-DQA1 genes do?

HLA-DRB1 and HLA-DQA1 encode surface proteins on immune cells that present foreign peptide fragments - such as pieces of allergen proteins - to T-helper cells. Variation in these genes influences how strongly and selectively the immune system responds to different allergens.

Is the evidence linking rs117222852 to allergies strong?

Both associations reached the genome-wide significance threshold (P < 5.0 × 10^-8), but the study was conducted in only 564 Japanese children and has not been replicated in an independent cohort. The findings are considered preliminary.

What is profilin sensitization?

Profilin is a structural protein found in many plants, including pollens, fruits, and vegetables. Immune sensitization to profilin can cause cross-reactive allergic responses across a wide range of plant-derived allergen sources.

What does GTEx data reveal about rs117222852?

GTEx eQTL data indicate the alternate allele of rs117222852 is associated with increased expression of HLA-DRB6 across multiple tissues (esophagus, heart, breast, adipose, thyroid) and increased expression of HLA-DQA2 in breast and esophageal tissue. These are expression-level signals and do not directly predict clinical outcomes.