Association of KIR2DL5, KIR2DS5, and KIR2DS1 allelic variation and Atopic Dermatitis

Abstract

Abstract Natural killer cells (NK) have been associated with the pathophysiology of atopic dermatitis (AD). NK function is regulated by killer cell Ig-like receptor family (KIR) receptors that interact with HLA ligands. The goal of this study was to focus on allelic variation in genes KIR2DL5, KIR2DS5, and KIR2DS1 with respect to AD. This was a case-control study of individuals with (n = 313) and without (n = 176) AD. Associations were estimated using logistic regression. Evaluations included interactions between KIR and known HLA ligand pairs. The prevalence of KIR2DL5 was 52.5% (95% CI: 48.0,57.0), KIR2DS5 was 33.0% (28.8,37.3), and KIR2DS1 was 33.6% (29.4,38.0). When compared to those who did not have KIR2DL5, homozygote individuals for KIR2DL5*001:01 were more likely to have AD (OR: 2.16 (95% CI:1.31,3.53) p = 0.0023). The effect of KIR2DL5*001:01 was similar in Whites and Blacks. The alleles from the other KIR genes of interest were not associated with AD. There is no known HLA ligand for KIR2DL5. However, the effect of KIR2DL5*001:01 increases in the presence of HLA-B *-21TT leader sequence (2.46(1.37,4.41) p = 0.0025) and HLA-C2 ligand (2.07 (1.37,4.41, p = 0.000002). This is the first study to explore KIR allelic variation in AD. KIR2DL5*001:01 allele is independently associated with an increased risk of AD.