The association between the IL-20-1723C→G allele on the 1q chromosome and psoriasis triggered or exacerbated by an upper respiratory tract infection in the Chinese Han population.

BACKGROUND: Psoriasis is a cutaneous disorder of multifactorial etiology influenced by both genetic and environmental factors such as infection. METHODS: We conducted a genome analysis with 20 microsatellite markers spanning the long arm of chromosome 1 in 36 Chinese families with psoriasis and detected evidence for linkage at 1q21 with a nonparametric linkage score of 1.74, p=0.03, and 1q32 with one of 1.84, p=0.03. According to the positional and functional candidate principle, we further investigated the single-nucleotide polymorphisms of the HAX-1 gene (located in 1q21) and IL-20 gene (located in 1q32) in a case-control study including 340 sporadic patients and 199 controls. RESULTS: We determined that the frequency of the G allele of IL-20-1723C→G (rs1713239) was significantly higher among psoriatic patients (38.5% in cases vs. 31.2% in controls, p=0.015, odds ratio, OR=1.39, 95% confidence interval, CI=1.07-1.80). When we stratified our analysis by psoriasis triggered or exacerbated by infection of the upper respiratory tract, a significant difference was detected (42.4% in stratified cases vs. 31.2% in controls, p=0.005, OR=1.63, 95% CI=1.15-2.30). CONCLUSION: We assume that triggered or exacerbated by respiratory tract infection, the population with the G allele of IL-20-1723C→G are predisposed to psoriasis.

The role of ERK1/2 signaling pathway in coronary microembolization-induced rat myocardial inflammation and injury.

AIM: Inflammation plays an important role in coronary microembolization (CME)-induced myocardial injury. The present study was designed to investigate the role of extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway in regulating myocardial inflammation and cardiac function in a rat model of CME. METHODS: Sprague-Dawley rats were randomly divided into three groups: sham-operated group (sham group), CME group and PD98059 group (15 animals per group). CME was produced by injection of 42-µm microspheres into the left ventricle with occlusion of the ascending aorta. Rats in the PD98059 group were injected with PD98059, a specific ERK1/2 inhibitor, 30 min before the CME operation. Western blotting and immunohistochemistry analysis were used to determine the activation of ERK1/2. Echocardiography was employed to evaluate cardiac function. Hematoxylin-eosin staining was performed to assay myocardial inflammation. Expression of TNF-α mRNA was determined by RT-PCR analysis, and activity of NF-κB was assessed by electrophoretic mobility shift assay. RESULTS: CME dramatically induced cardiac dysfunction (left ventricular ejection fraction, LVEF, was 72.97 ± 3.20% in the CME vs. 82.69 ± 3.50% in the sham group, p < 0.05) and local myocardial inflammatory response, both of which were ameliorated significantly by PD98059 (LVEF was 76.46 ± 4.46 and p < 0.05 vs. CME group). When compared to the CME group, PD98059 markedly attenuated the increased phosphorylation of ERK1/2 (0.48 ± 0.11 vs. 0.92 ± 0.10, p < 0.05), expression of TNF-α mRNA (0.42 ± 0.06 vs. 0.94 ± 0.04, p < 0.05) and activity of NF-κB (104.83 ± 13.65 vs. 540.79 ± 24.95, p < 0.05) in CME rat myocardium. CONCLUSIONS: The present study demonstrates a novel role of the ERK1/2 signaling pathway in promoting myocardium inflammation and dysfunction in CME, and suggests that ERK1/2 is a novel potential therapeutic target for CME.