Premium
A Genome‐Wide Association Study of Plasma α 2 ‐Macroglobulin Concentrations in Young Adults
Author(s) -
Jamnik Joseph,
Borchers Christoph,
ElSohemy Ahmed
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.127.3
Subject(s) - genome wide association study , single nucleotide polymorphism , gluten , macroglobulin , population , genotyping , genetic association , disease , biology , immunology , medicine , genetics , gene , genotype , food science , environmental health
Background Gluten intake has been shown to be associated with circulating levels of α 2 ‐macroglobulin in young adults without celiac disease. Gluten‐free foods have increased in popularity over the past decade despite a poor understanding of the physiological effects of gluten intake in those without celiac disease. Plasma α 2 ‐macroglobulin represents a physiologically important molecule involved in inflammation and cytokine release, but the contribution of common genetic variation to the observed variation in circulating concentrations of α 2 ‐macroglobulin remains unclear. Objective The objective was to identify genetic variants that are associated with α 2 ‐macroglobulin in a population of young adults using a genome‐wide approach. Methods A genome‐wide association study (GWAS) was conducted on circulating levels of α 2 ‐macroglobulin in a population of young Caucasians without clinically diagnosed celiac disease from the Toronto Nutrigenomics and Health Study (n=488). Concentrations of α 2 ‐macroglobulin were measured in plasma using a multiple reaction monitoring HPLC‐MS/MS assay. Genome‐wide genotyping was conducted for 822,000 single nucleotide polymorphisms (SNPs) using the Affymetrix 6.0 chip. The association between genome‐wide genetic variants and plasma α 2 ‐macroglobulin was explored using linear regression with an additive mode of inheritance. Results Circulating α 2 ‐macroglobulin was associated with variation in ICOSGL (p = 3.9×10 −7 ), a T‐cell stimulatory gene involved in cytokine release and various immune‐related disorders including celiac disease. Conclusion These results suggest that the physiological effects of gluten intake may be mediated by genes involved in T‐cell proliferation and cytokine release. Support or Funding Information Research support from the Advanced Foods and Materials Network.