Candidate gene analysis of asthma in a population of Arab descent: a case-control study in Jordan
PERSONALIZED MEDICINE
Authors: Almomani, Basima A.; Al-Eitan, Laith N.; Samrah, Shaher M.; Al-Quasmi, Mohammed N.; McKnight, Amy J.
Abstract
Aim: To evaluate whether SNPs (n = 15) in ten candidate genes (ADRB2, ADH5, ARGI, CRHR1, STIP1, LTA4H, LTC4S, ALOX5, ABCC1 and OATP2B1) are associated with asthma in Jordanian population of Arab descent. Methods: A case-control study included 245 adult asthmatics and 249 controls. Results: Significant genetic association was identified at the rs2236647 (T/C) SNP in STIP1 and risk of asthma (p < 0.001). The C allele and CC genotype of this SNP were significantly higher in asthmatics compared with controls. The rs1141370 SNP (Val34Met) in ADRB2 is not polymorphic in our cohort. Conclusion: The rs2236647 SNP could act as a reliable tool to identify individuals at risk of developing asthma and provision of early intervention in population of Arab descent.
Lazaroid (U-74389G) ameliorates lung injury due to lipid peroxidation and nitric oxide synthase-dependent reactive oxygen species generation caused by remote systematic ischemia-reperfusion following thoracoabdominal aortic occlusion
INTERNATIONAL JOURNAL OF SURGERY
Authors: Perlikos, Fotis; Lagiou, Maria; Papalois, Apostolos; Rizou, Tatiana; Kroupis, Christos; Toumpoulis, Ioannis K.
Abstract
Introduction: Lung ischemia-reperfusion injury after thoracoabdominal aortic occlusion represents a major complication, which increases morbidity and mortality. In the present study we hypothesized that lazaroid U-74389G intravenous administration protects from lung ischemia-reperfusion injury through lipid peroxidation inhibition. Materials and methods: A total of 24 pigs were randomized in three groups. Group I (n = 8) underwent sham operation, group II (n = 8) underwent thoracoabdominal aortic occlusion for 45min and received placebo and group III (n = 8) received 3 doses of lazaroid (3 mg/kg) 60 and 30min before thoracoabdominal aortic occlusion and at 30min during thoracoabdominal aortic occlusion (duration 45min). Aortic occlusion was performed with aortic balloon-catheters under fluoroscopic guidance. All animals were sacrificed at the 7 t h postoperative day and lung specimens were harvested for molecular analysis. Results: mRNA levels of leukotrienes LB4 (LTB4R2), LC4 (LTC4S) and nitric oxide synthase (NOS) isoforms including iNOS, nNOS and eNOS were determined with real-time RT-qPCR. Nitric oxide can either induce (iNOS) or inhibit (nNOS and eNOS) lipid peroxidation based on its specific isoform origin. Group III showed significantly reduced mRNA levels of LTB4R2 (-63.7%), LTC4S (-35.9%) and iNOS (-60.2%) when compared with group II (P < 0.05, for all). The mRNA levels of nNOS was significantly increased (+ 37.4%), while eNOS was slightly increased (+ 2.1%) in group III when compared with group II (P < 0.05 and P = 0.467 respectively). Conclusion: Lazaroid U-74389G may represent an effective pharmacologic intervention in reducing lung ischemia-reperfusion injury following thoracoabdominal aortic occlusion.