Adulthood-onset celiac disease is associated with intercellular adhesion molecule-1 (ICAM-1) gene polymorphism

Celiac disease (CD) is a multifactorial T-cell-mediated autoimmune disease characterized by gluten-triggered villous atrophy and malabsorption. Although human leukocyte antigen (HLA) class II genes are strong susceptibility factors, non-HLA genes likely contribute to most of CD predisposition. The intercellular adhesion molecule-1 (ICAM-1) gene is a good candidate for CD predisposition because its encoded protein acts as an adhesion and costimulatory receptor. Two single-base polymorphisms (G/A in exon 4 encoding G241R, and A/G in exon 6 encoding K469E) were analyzed in 180 French Caucasian CD case patients (110 patients diagnosed before the age of 15 and 70 patients after the age of 18), and 212 French Caucasian healthy controls. The R241 allele frequency was increased in CD case patients compared with controls (14.2% vs. 5.4% respectively, p = 0.000015, odds ratio [OR] for the R241 allele = 2.9, 95% confidence intervals [CI] = 1.7-4.8). After stratifying for age of disease onset, the R241 variant mainly conferred predisposition to CD occurring during adulthood (OR = 4.2, 95% CI = 2.3-7.5, Pc = 0.000004 for adulthood-onset CD vs. R = 2.1, 95%, CI = 1.2-3.9, Pc = 0.0047 for childhood-onset CD). Position 241 of ICAM-1 maps to the binding site for the integrin Mac-1 and might modify the strength of interaction between endothelium and immune cells. If confirmed in independent datasets, these results may be of importance in at-risk individuals to distinguish rapid from delayed progression to clinical CD.