Juvenile Adamantiades-Behçet Disease.

Adamantiades-Behçet disease (ABD) is a chronic, multisystemic, recurrent, inflammatory vascular disorder of unknown etiology. Patients with symptoms initially appearing at the age of 16 or less are considered as cases of juvenile-onset ABD (JABD). JABD is relatively rare compared to ABD of adults, and only case reports and case studies have been published regarding this subtype of the disease. Epidemiology, clinical features, diagnosis and treatment of JABD are discussed in this review.

Iron metabolism gene expression in human skeletal muscle.

Little is known about iron metabolism in skeletal muscle while hepatic iron metabolism is well understood. The aim of this study is to compare the iron metabolism gene expression profile in skeletal muscle and the liver in humans. Muscle and hepatic biopsies from six normal individuals were acquired. Twelve genes involved in iron metabolism( import, storage, export) were selected to be studied. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed in order to determine the expression profile in skeletal muscle and compare it to the one from the liver. Semi-quantification of the gene expression in the studied tissues was performed by densitometric analysis (DA). The results were expressed relative to the percentage of the ß-actin gene. Fine analysis was performed by real-time PCR (q-PCR) quantification for the genes that their expression presented a difference of more than 20% in the 2 tissues in the first applied densitometric analysis. Most of the studied genes, HJV, TFR1, HFE, DMT1, DMT1nonIRE, NGAL, HEPH, IREG1, FTH1 were well expressed (>70% of ß-actin) in skeletal muscle . HAMP, CP, and TFR2 were absent or minimally expressed (<10% of ß-actin) in skeletal muscle while they were well expressed in liver. HJV and Heph were found to have higher expression in skeletal muscle (SM) compared to liver (L) (SM/L=2.65 ± 1.1(p<0.05) and SM/L=1.5 ± 0.06(p<0.05 respectively in q-PCR). The relative expressions of the studied genes in both tissues and their relative contribution in iron homeostasis in different pathways are discussed.

The effect of the plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk.

Plasminogen activator inhibitor (PAI-1), is the central component of the fibrinolytic system. A deletion/insertion (4G/5G) polymorphism in the promoter region of the PAI-1 gene has been correlated with levels of plasma PAI-1. The 4G allele is associated with higher levels of PAI-1, and might increase the risk for intravascular thrombosis. However, the contribution of this genetic variant to the risk for thrombosis, both arterial and venous, has not been clearly established. A broad spectrum of findings regarding the effect of the 4G allele on thrombotic risk in different target organs has been reported. Our aim is to summarize the variable influence of this polymorphism on thrombotic events in different tissues or organs and explain the underlying mechanisms accounting for these differences.

Integrin, alpha 2 gene C807T polymorphism and risk of ischemic stroke: a meta-analysis.

INTRODUCTION: Platelet adhesion to fibrillar collagen via the membrane glycoprotein (GP) Ia/IIa (alpha2beta1), is a crucial event in the pathogenesis of arterial occlusive disorders. The C807T single nucleotide polymorphism of the integrin, alpha 2 (ITGA2) gene has been shown to correlate with the platelet GPIa/IIa density. Consequently, subjects with the 807T allele, who express the highest receptor density, might have an increased potential of platelet adhesion and, hence an increased risk of cerebrovascular disease. However, the research findings remain controversial. MATERIALS AND METHODS: A comprehensive electronic search was carried out up until November 2005 and 7 independent studies with a maximum of 774 cases and 1074 controls were analyzed using random effects models. RESULTS: The pooled frequency of the T allele was 36.33% in cases and 37.01% in controls. The T versus the C allele contrast gave an OR of 1.11 (95% confidence interval=0.827-1.499). All the other comparisons failed to show any significant result. Age, sex, and cardiovascular risk factors were included as covariates into a meta-regression model without a significant finding. CONCLUSIONS: This meta-analysis do not support an association between the C807T polymorphism of ITGA2 gene and stroke, but given the significant between study heterogeneity and the small number of studies, the summary effect should be interpreted carefully.

Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of ischemic stroke: a meta-analysis.

This study investigated the hypothesis that the insertion/deletion (4G/5G) polymorphism of the plasminogen activator inhibitor type-1 gene affects the risk for ischemic stroke, since results concerning this association have been controversial. We therefore performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out until January 2006. The analysis was performed using random-effects models and meta-regression. Eighteen eligible studies were retrieved (15 case-control studies and three cohort studies). The case-control studies included 3104 cases and 4870 control individuals concerning the contrast of 4G/4G versus remaining genotypes. The 4G pooled allele frequencies in cases and controls were 54.21 and 54.75%, respectively. Overall, the per-allele odds ratio of the 4G allele was 0.98 (95% confidence interval, 0.858-1.121). Regarding genotypes, we derived nonsignificant odds ratios in all contrasts. The subanalysis including the three studies with a prospective design in the 4G/4G versus 5G/5G contrast derived a significant result (relative risk, 0.523; 95% confidence interval, 0.353-0.775), but the estimated effect size was insignificant when cohort and case-control studies were analyzed together (relative risk, 0.848; 95% confidence interval, 0.662-1.087). We failed to demonstrate a significant association between the 4G/5G polymorphism and ischemic stroke under basal conditions. Determination of plasminogen activator inhibitor type-1 function seems of much higher clinical value than determination of the 4G/5G polymorphism. The effect of this genotype on risk of ischemic stroke in acute stressful diseases and the role of cohort studies in genetic epidemiology, however, warrant further investigation.

The AGT and the GNB3 polymorphisms and insulin resistance in prehypertension.

OBJECTIVE: This study surveyed the frequencies of single nucleotide polymorphisms (SNPs) M235T AGT and C825T GNB3, and their association with insulin resistance, other biochemical markers and qualitative variables in subjects with high normal blood pressure and/or prehypertension in the Greek population. DESIGN: 330 men and women of Greek origin were divided into 3 groups: a) hypertensive, b) prehypertensive and c) control group. These groups were genetically tested for these polymorphisms and insulin resistance with the HOMA index. RESULTS: No statistically significant differences were found among the polymorphisms of the compared groups. However, the ? allele carriers (CT/TT vs. CC) of the C825T polymorphism were associated with an increased BMI in all 3 groups (p=0.004). The HOMA index was higher in the hypertensive (p=0.006) and prehypertensive (p=0.016) versus the control group, and similar results were found for insulin (hypertensive vs. control p=0.012, prehypertensive vs. control p=0.001) without statistical significance between the first 2 groups (p=0.522). Additionally, there was a statistically significant difference between the control group and the hypertensive and prehypertensive groups regarding cholesterol (control vs. hypertensive p=0.001, control vs. prehypertension p=0.018) and triglycerides (control vs. hypertensive p=0.0001, control vs. prehypertension p=0.007). Differences were also noted between the control and the hypertensive group regarding the value of HDL (p=0.005) and LDL (p=0.013). CONCLUSION: This study failed to demonstrate a correlation between specific SNPs, blood pressure and insulin resistance in the 3 groups. However, T allele carriers of the polymorphism C825T were found to have an increased BMI. Similarly, increased insulin resistance and lipidemia were more common in the hypertensive and prehypertensive populations.

Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and coronary artery disease: a meta-analysis.

BACKGROUND: The platelet-collagen receptor, glycoprotein (GP) la/lla plays a crucial role in the adhesion of platelets to fibrillar collagen, an event contributing to the pathogenesis of thrombosis. The C807T polymorphism of the GPla gene is considered a genetic marker of the platelet GPla/lla density. The importance of the GPla gene C807T polymorphism as a genetic risk factor for coronary artery disease (CAD) remains controversial. To assess this association, we performed a meta-analysis of published data. METHODS: A comprehensive meta-analysis of 19 studies, with a total sample of 13835 subjects using random effects models. RESULTS: The C versus T allele contrast gave an OR of 0.998 with 95% Cl 0.937-1.064. Similarly, comparing the C homozygotes with the T homozygotes, the CC genotype versus the others and the TT genotype versus the rest, no evidence of any gene-disease association was obtained. Furthermore, the meta-regression analysis did not disclose any variable that could modify the role of this polymorphism in the development of CAD. CONCLUSION: Our findings support the view that C807T polymorphism of the GPla gene is not a significant risk factor for CAD, either alone or in combination with other major cardiovascular risk factors.