Interleukin-1β (IL-1β) & IL-4 gene polymorphisms in patients with systemic lupus erythematosus (SLE) & their association with susceptibility to SLE.

Background & objectives: Interleukin-1 (IL-1) is one of the pro-inflammatory cytokines that plays a main role in the regulation of immune and inflammatory responses. Interleukin 4 (IL-4) as an anti-inflammatory cytokine regulates balance between Th1 and Th2 immune responses. This study was undertaken to investigate the IL-1β and IL-4 genes polymorphisms in patients with systemic lupus erythematosus (SLE) and also association between the polymorphisms and susceptibility to SLE. Methods: One hundred and sixty three SLE patients and 180 healthy controls were genotyped for the IL-4 VNTR (variable number tandem repeat), IL-1β C-511T and IL-1β T-31C polymorphisms by polymerase chain reaction (PCR) or PCR-RFLP (restriction fragment length polymorphism) method. Results: The frequencies of CC genotype and C allele of the IL-1β T-31C polymorphism were significantly (P<0.01) lower in SLE patients than controls. Moreover, the frequencies of RP1/RP2 genotype and RP2 allele of IL-4 VNTR polymorphism were significantly (P<0.05) higher in the SLE patients. No association was observed between IL-1β C-511T polymorphism and increased risk of SLE. We observed increased frequency of CT and TT genotypes of IL-1β C-511T polymorphism in SLE patients with malar rash compared to SLE patients without this manifestation. Interpretation & conclusions: The present findings suggest that IL-1β T-31C and IL-4 VNTR polymorphisms but not IL-1β C-511T polymorphism may contribute in SLE pathogenesis. In addition, CT and TT genotypes of IL-1β C-511T polymorphism were associated with SLE.

Activity of antioxidant enzymes in seminal plasma and their relationship with lipid peroxidation of spermatozoa

PURPOSE: To determine the activity of seminal plasma catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) and their relationship with malondialdehyde (MDA), as a marker of lipid peroxidation, content of spermatozoa and seminal plasma in normozoospermic and asthenozoospermic males. MATERIALS AND METHODS: Semen samples were obtained from 15 normozoospermic and 30 asthenozoospermic men. RESULTS: We observed inverse correlations between activities of CAT (k/mL) and SOD (U/mL) in seminal plasma with MDA content of spermatozoa from normozoospermic samples (r =- 0.43, p < 0.05 and r =- 0.5, p < 0.05, respectively). Significant correlations were observed between total activity CAT (k/total seminal plasma) with total SOD (U/total seminal plasma) and GPX activity (mU/total seminal plasma) in seminal plasma from normozoospermic samples (r = 0.67, p = 0.008 and r = 0.455, p = 0.047, respectively). Furthermore, we found positive correlations between total activities of CAT, SOD and GPX with total content of MDA in seminal plasma (nmoL/total seminal plasma) from normozoospermic samples (r = 0.67, p = 0.003; r = 0.73, p = 0.003; r = 0.74, p = 0.004, respectively). In asthenozoospermic samples, there were no significant correlations observed between activities of CAT (k/mL), SOD (U/mL) and GPX (mU/mL) of seminal plasma with MDA content of spermatozoa. However, we found significant correlations between total activities of CAT (k/total seminal plasma) and SOD (U/total seminal plasma) with total content of MDA in seminal plasma (r = 0.4, p = 0.018 and r = 0.34, p = 0.03, respectively). CONCLUSION: These findings indicate a protective role for antioxidant enzymes of seminal plasma against lipid peroxidation of spermatozoa in normozoospermic samples.

Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with coronary artery disease in Iran.

BACKGROUND & OBJECTIVES: Endo-derived nitric oxide (NO) is synthesized from L-arginine by endothelium nitric oxide synthase (eNOS) encoded by the NOS3 gene on chromosome7. Since reduced NO synthesis has been implicated in the development of coronary atherosclerosis; polymorphisms of NOS gene might be associated with increased susceptibility to this disorder and coronary artery disease (CAD). We therefore undertook this study to determine the association between the occurrence of CAD and eNOS4 b/a polymorphism in Iranian patients. METHODS: We studied the 27 base pair tandem repeat polymorphism in intron4 of the endothelial nitric oxide synthase (eNOS) gene in 141 unrelated CAD patients with positive coronary angiograms and 159 age matched control subjects without a history of symptomatic CAD. The eNOS gene intron4a/b VNTR polymorphism was analyzed by polymerase chain reaction. The plasma lipids levels and other risk factors were also determined. RESULTS: The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 68.8, 29.1 and 2.1 per cent in CAD subjects, and 81, 18.4 and 0.6 per cent in control subjects, respectively. The genotype frequencies differed significantly (P<0.05) between the two groups. The frequency of the a allele was 16.7 per cent in CAD subjects and 9.8 per cent in control subjects and was significantly higher in the patients (P<0.05, Odds ratio=1.84). Plasma lipids, except HDL-C were also significantly increased in CAD group. INTERPRETATION & CONCLUSION: Though the genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a, also 'a' allele frequency differed significantly between the CAD patients and controls, this polymorphism was not an independent risk factor for the development of CAD in Iranian patients. Further studies with larger samples need to be done to confirm these findings.