Background/Aims: The C1431T polymorphism of peroxisome proliferator activated receptor-γ (PPAR-γ) gene is related to diabetes and metabolic-syndrome. However, studies have been inconclusive about its association with coronary artery disease (CAD) and there have been no studies analyzing the association of this polymorphism with fasted-serum-lipid levels in Iranian-individuals with CAD. We investigated the association of PPAR-γ C1431T-polymorphism with CAD and dyslipidaemia in 787 individuals. Methods: Anthropometric-parameters and biochemical-measurements were evaluated, followed by genotyping. The association of the genetic-polymorphisms with CAD and lipid-profile was determined by univariate/multivariate-analyses. Results: Patients with CT or CT+TT genotype were at an increased-risk of CAD relative to CC-carriers (adjusted odds ratio: 2.03; 95% confidence interval, 1.01-4.09; p = 0.046). However, in the larger population, CT genotype was present at a higher frequency in the group with a positive angiogram. Furthermore, CT+TT genotypes were associated with an altered fasted-lipid-profile in the initial population sample of patients with a positive angiogram, compared to the group with a negative-angiogram. The angiogram-positive patients carrying the T allele had a significantly higher triglyceride, serum C-reactive protein and fasting-blood-glucose. Conclusion: We have found the PPAR-γ C1431T polymorphism was significantly associated with fasted serum lipid profile in individuals with angiographically defined CAD. Since accumulating data support the role of PPAR-γ polymorphisms in CAD, further studies are required to investigate the association of this polymorphism with coronary artery disease.

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Background: Intervening sequences (introns) have significant effects on genomic regulations and molecular evolution. So, it deserves a deeper analysis for better understanding the possible regulatory roles of these regions. Objective and Method: Accordingly, the intron 2 (In-2) of the human B-cell lymphoma 2 (hBcl2) gene, with regard to the size of the In-2 as well as critical roles of the gene in the homeostatic of the cellular balance, was analyzed by using in-silico approaches to identify In-2 transcription factor binding (In2-TFBs) motifs. Results: Our analysis revealed 966 motifs of 118 different TFBs types which were scattered throughout both the strands of the complete sequence of the gene, in particular on the In-2, with significant pattern of distribution and repetition. Distribution pattern of these motifs revealed that most of them were accumulated in narrow regions of the In-2, far from the area of the splicing sites. Moreover, it was observed that except for WT1-TFBs, Gfi-1-TFBs, GAGA-TFBs, all other motifs were sporadic, with irregular and random distribution. Among these motifs, WT1-TFBs showed the highest frequencies which were situated in four neighboring regions of the In-2, by a close linear relationship to Sp1-TFBs. Furthermore, the sequence logos of the WT1-TFBs showed that they ranged in size from 22 up to 45 bps and were enriched with G and T nucleotides. Meanwhile, the binding affinity of WT1-TF to WT1-TFBs revealed significant differences compared to the other sequences of the gene as negative control. Conclusion: In general, this data provides supporting evidences for the existence of regulatory regions in the intronic sequences of the hBcl2 gene especially in the In-2, and also represents new targets for WT1-TF which might contribute to hBcl2 regulation and apoptosis process.

In this study, we have re-evaluated how EBV status influences clinical outcome. To accomplish this, we performed a literature review of all studies that have reported the effect of EBV status on patient outcome and also explored the effect of EBV positivity on outcome in a clinical trial of children with cHL from the UK. Our literature review revealed that almost all studies of older adults/elderly patients have reported an adverse effect of an EBV-positive status on outcome. In younger adults with cHL, EBV-positive status was either associated with a moderate beneficial effect or no effect, and the results in children and adolescents were conflicting. Our own analysis of a series of 166 children with cHL revealed no difference in overall survival between EBV-positive and EBV-negative groups (p = 0.942, log rank test). However, EBV-positive subjects had significantly longer event-free survival (p = 0.0026). Positive latent membrane protein 1 (LMP1) status was associated with a significantly lower risk of treatment failure in a Cox regression model (HR = 0.21, p = 0.005). In models that controlled for age, gender, and stage, EBV status had a similar effect size and statistical significance. This study highlights the age-related impact of EBV status on outcome in cHL patients and suggests different pathogenic effects of EBV at different stages of life.

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