Lack of association of ALOX12 and ALOX15B polymorphisms with psoriasis despite altered urinary excretion of 12(S)-hydroxyeicosatetraenoic acid

BACKGROUND Pro- and anti-inflammatory metabolites of arachidonic acid - eicosanoids - participate in skin homeostasis, affecting the growth and differentiation of keratinocytes. Alterations of 12-lipoxygenase (LOX) and 15-LOX and their metabolites have been described in the epidermis of patients with psoriasis, but systemic production of 12-LOX and 15-LOX eicosanoids has not been studied in the disease. OBJECTIVES To ascertain the frequencies of the genetic variants ALOX12 rs1126667 and ALOX15 rs11568070 in cases and controls, and to compare urinary metabolites of 12(S)-hydroxyeicosatetraenoic acid (HETE) between patients with psoriasis and healthy controls. METHODS Patients with psoriasis (n = 200) were stratified depending on the severity of their dermal lesions. Genotyping was performed using a 5'-nuclease real-time assay. The concentrations of 12(S)-HETE, its metabolites and 15(S)-HETE were determined in urine samples using high-performance liquid chromatography-tandem mass spectrometry. RESULTS Tetranor-12(S)-HETE metabolite excretion was significantly higher in urine of patients with psoriasis, while excretion of 12(S)-HETE was decreased. Neither 12(S)-HETE nor tetranor-12(S)-HETE correlated with the type of disease or severity score. No difference in urinary 15(S)-HETE was found between the study groups. Genotype distribution of the ALOX12 rs1126667 or ALOX15 rs11568070 polymorphisms did not discriminate for the disease or its severity. CONCLUSIONS Systemic metabolism of 12(S)-HETE is accelerated in psoriasis because excretion of the tetranor-12(S)-HETE inactivation product is elevated. No correlation with the severity or extent of psoriasis is detectable. We propose that in patients with psoriasis, 12(S)-HETE to tetranor-12(S)-HETE conversion could be at least a marker for this disease, in which inflammation of the skin can induce microsomal beta-oxidation of this eicosanoid.