Correlation between intracellular interferon-γ (IFN-γ) production by CD4+ and CD8+ lymphocytes and IFN-γ gene polymorphism in patients with type 2 diabetes mellitus and latent autoimmune diabetes of adults (LADA)

IFN-γ is considered to be involved in the pathogenesis of diabetes mellitus. In this study, the presence of T/A mutation at position -874 in IFN-γ gene was assessed in patients with latent autoimmune diabetes of adults (LADA), in patients with type 2 diabetes and in healthy individuals. Subsequently, an attempt was made to correlate the presence of this mutation with the ability of CD4+ or CD8+ lymphocytes from these individuals to release IFN-γ following mitogenic stimulation. There were no significant differences in the distribution of genotypes and haplotypes in the three study groups. However, the frequency of the low IFN-γ production allele (IFN-γ 874*A) was significantly higher in type 2 diabetics compared to controls. CD4+ and CD8+ cells obtained from type 2 diabetics released significantly lower amounts of IFN-γ in the intracellular space, compared to those released by cells obtained from LADA patients and healthy volunteers. Furthermore, even CD4+ and CD8+ from type 2 diabetics bearing the TT genotype (high producers) released significantly lower amounts of IFN-γ than LADA patients carrying the same genotype, probably due to the activity of molecules directly or indirectly inhibiting IFN-γ production. The results of this study indicate that IFN-γ may contribute to the development of type 2 diabetes, based on a combination of molecular and immunological observations. © 2005 Elsevier Ltd. All rights reserved

TNF-α, TGF-β1, IL-10, IL-6, gene polymorphisms in latent autoimmune diabetes of adults (LADA) and type 2 diabetes mellitus

Abundant evidence suggests that cytokines involve in the pathogenesis of latent autoimmune diabetes of adults (LADA). This is a slowly progressive form of type 1 diabetes, which is initially diagnosed as type 2 diabetes. In this study, healthy individuals LADA and type 2 diabetic patients were genotyped for IL-6-174G/C, TNF-α-308A/G, TGF-β1-codon10T/C, TGF-β1-codon25G/C, IL-10-1082A/G, IL-10-819T/C, IL-10-592A/C gene polymorphisms, by sequence-specific-primer polymerase chain reaction methodology. A significant difference in the frequencies of -1082A/G IL-10 alleles was observed, with the -1082*A allele (known to be associated with low IL-10 production), predominating in LADA diabetics than type 2 diabetics (p=0.036). No significant differences of genotypes, phenotypes, or haplotype frequencies in the remaining cytokine polymorphisms were observed. Analysis of allele combinations revealed a significant involvement of the low and high in vitro production IL-10 alleles in the development of LADA and type 2 diabetes, respectively. These results suggest that the G/A mutation at position -1082 of IL-10 promoter gene region might be one of the factors participating to the pathogenesis of LADA diabetes and that identification of cytokine gene polymorphisms might contribute to the characterization of the different types of diabetes mellitus. © 2004 Springer Science+Business Media, Inc

High homocysteine and low folate concentrations in acute aortic dissection

Background: Biomarkers for monitoring progression and prognosis of thoracic aneurysm are of great interest. Homocysteine (Hcy) induces elastolysis in arterial media and may directly affect fibrillin-1 or collagen whereas lipoprotein (Lp) (a) inhibits elastolysis by reducing activation of matrix metallopeptidase-9. Methods: We studied 31 consecutive patients with acute aortic dissection (AAD) admitted for emergency surgery (group I, 60 ± 13 years old, 25 men), 30 consecutive patients with chronic aneurysms of the ascending aorta (group II, 67 ± 12 years old, 24 men) and 20 healthy controls (group III, 58 ± 15 years old, 14 men). We evaluated Hcy, folate, B12, Lp(a) and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism at baseline. Results: Hcy, folate and B12 differed significantly among the 3 studied groups (P = 0.016, P = 0.004 and P = 0.001, respectively). The levels of Hcy and B12 were significantly higher in group I compared to both groups II and III (P = 0.05 and P = 0.002, P < 0.001 and P = 0.017, respectively) and without significant differences between groups II and III (P = 0.083 and P = 0.124). Folate was significantly lower in group I compared to both groups II and III (P = 0.001 and P = 0.006, respectively) and without marked difference between groups II and III (P = 0.409). No significant difference was found in serum levels of Lp (a) (P = 0.074) or among the frequency of MTHFR C677T genotypes. Conclusions: Patients with AAD present with higher Hcy and lower folate compared to both chronic aneurysms and controls. © 2012 Elsevier Ireland Ltd. All rights reserved

Osteopontin in relation to Prognosis following Coronary Artery Bypass Graft Surgery

Cardiovascular events may occur even after complete revascularization in patients with coronary artery disease. We measured preoperative osteopontin (OPN) levels in 131 consecutive patients (66.5 ± 10 years old, 117 men and 14 women) with left ventricular ejection fraction of 50.7 ± 9.2 % and low logistic EuroScore (3.5 ± 3.2 %) undergoing elective Coronary Artery Bypass Grafting (CABG) surgery. Patients were prospectively followed up for a median of 12 months (range 11-24). The primary study endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, need for repeat revascularization, and hospitalization for cardiovascular events. Pre-op OPN plasma levels were 77.9 (49.5, 150.9). Patients with prior acute myocardial infarction (AMI) had significantly higher OPN levels compared to those without [131.5 (52.2, 219) versus 73.3 (45.1, 125), p = 0.007 ]. OPN levels were positively related to EuroScore (r = 0.2, p = 0.031). Pre-op OPN levels did not differ between patients who had a major adverse event during follow-up compared to those with no event (p = 0.209) and had no effect on the hazard of future adverse cardiac events [HR (95% CI): 1.48 (0.43-4.99), p = 0.527 ]. The history of AMI was associated with increased risk of subsequent cardiovascular events at follow-up (p = 0.02). OPN is associated with preoperative risk assessment prior to low-risk CABG but did not independently predict outcome. © 2016 Eftihia Sbarouni et al

Cytokine gene polymorphisms are associated with markers of disease severity and prognosis in patients with idiopathic dilated cardiomyopathy

Aims: To identify potential genetic associations of five cytokine gene polymorphisms with disease severity and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). Methods and results: Eighty patients with DCM were genotyped for transforming growth factor beta1 (TGF-β1)+869 T/C (codon10 Leu→Pro), TGF-β1+915 G/C (codon25 Arg→Pro), interleukin (IL)-6 -174G/C, tumor necrosis factor-alpha (TNF-α) -308A/G, interferon-gamma (IFN-γ)+874T/A, IL-10 -1082A/G, IL-10 -819T/C and IL-10 -592A/C gene polymorphisms. In homozygous TT patients for TGF-β1 +869 T/C polymorphism mean VO 2 max was significantly higher than in CC homozygous patients (25.67±6.73ml/kg/min vs. 20.29±6.35ml/kg/min, p=0.046), which remained significant only for patients younger than 39years old after adjusting for age and sex (p=0.009). C carriers of TGF-β1 +915 G/C polymorphism are 4.2 times more likely to be in a worse NYHA stage (III-IV) than non C carriers [OR: 4.25, 95% CI (1.53-11.80), p=0.006]. Patients GG homozygous for IL-6 -174G/C polymorphism presented greater left ventricle end-systolic (p=0.018) and end-diastolic (p=0.04) diameters in comparison to the CC homozygous. The AA homozygote for IFN-γ+874T/A polymorphism (p=0.02) and the combination of the TGF-β1+869 T/C and TGF-β1+915 G/C genotypes were associated with adverse outcome (p=0.014). Conclusion: Specific cytokine gene polymorphisms seem to be associated with worse prognosis as well as with measures of disease severity in DCM. © 2011 Elsevier Ltd