Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, P(combined) = 3.15 × 10(-9), odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, P(combined) = 3.0 × 10(-8), OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, P(combined) = 5.90 × 10(-12), OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10(-5), OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.

Background: Purinergic signaling regulates neutrophil activation. The source of ATP required for this process is unknown. Results: Mitochondria form the ATP that initiates purinergic signaling, and glycolysis provides the ATP that sustains functional responses of activated neutrophils. Conclusion: Mitochondrial ATP has a central role in triggering neutrophil activation. Significance: Mitochondria are regulators of the innate immune defense provided by neutrophils.

Background: Chemotaxis requires excitatory and inhibitory signals at the front and back of cells. PANX1 and P2Y 2 receptors provide local excitation at the front. Results: We found that PANX1 triggers A 2A receptor activation and inhibits chemotactic signaling at the back. Conclusion: PANX1 thus integrates excitatory and inhibitory signals that regulate chemotaxis at the front and back of cells. Significance: These findings suggest new strategies to modulate neutrophil chemotaxis.