Age of onset of myocardial infarction: is promoter polymorphism of the RAGE gene implicated?

Receptor for advanced glycation endproducts (RAGE) is a cell-surface molecule member of the immunoglobulin superfamily and engages differing ligands relevant to distinct processes. A growing body of evidence has suggested that RAGE may promote vascular inflammation through several mechanisms. The objective of this study was to identify the possible relationship between the -374 T/A polymorphism of the RAGE gene, myocardial infarction (MI), and its age of onset. A total of 691 MI patients and 234 matched controls were investigated. In this study, the frequency of the A allele and AA genotype of the -374 T/A promoter polymorphism is significantly lower in patients with MI respect to the control group (p < 0.01). Our results showed a significant role of the AA genotype on age of onset of MI. In particular, the mean age of the first MI was higher in patients with the AA genotype as compared to those that were AT or TT genotype carriers (p = 0.002). The relationship between -374 T/A RAGE polymorphism and age for the appearance of MI was independently related to common risk factors of disease (p < 0.01). Kaplan-Meier curves confirmed that subjects with the AA genotype have a later development of MI (p = 0.0022). This study is the first to investigate the role of RAGE polymorphisms on the susceptibility to develop the acute coronary events in the Italian population and identified this polymorphism as an age-related factor for MI development. The homozygous AA genotype may exert a protective role against the early development of MI

Age of Onset of Myocardial Infarction: Is Promoter Polymorphism of the RAGE Gene Implicated?

Receptor for advanced glycation endproducts (RAGE) is a cell-surface molecule member of the immunoglobulin superfamily and engages differing ligands relevant to distinct processes. A growing body of evidence has suggested that RAGE may promote vascular inflammation through several mechanisms. The objective of this study was to identify the possible relationship between the -374 T/A polymorphism of the RAGE gene, myocardial infarction (MI), and its age of onset. A total of 691 MI patients and 234 matched controls were investigated. In this study, the frequency of the A allele and AA genotype of the -374 T/A promoter polymorphism is significantly lower in patients with MI respect to the control group (p < 0.01). Our results showed a significant role of the AA genotype on age of onset of MI. In particular, the mean age of the first MI was higher in patients with the AA genotype as compared to those that were AT or TT genotype carriers (p = 0.002). The relationship between -374 T/A RAGE polymorphism and age for the appearance of MI was independently related to common risk factors of disease (p < 0.01). Kaplan-Meier curves confirmed that subjects with the AA genotype have a later development of MI (p = 0.0022). This study is the first to investigate the role of RAGE polymorphisms on the susceptibility to develop the acute coronary events in the Italian population and identified this polymorphism as an age-related factor for MI development. The homozygous AA genotype may exert a protective role against the early development of MI

Studio dei polimorfismi nel gene del recettore dell’apelina in pazienti con e senza ipertensione arteriosa

Apelina è un peptide endogeno che aumenta l’inotropismo cardiaco attraverso l’interazione con il suo recettore APJ. Alcuni risultati indicano che il sistema apelinergico possa avere un ruolo fisiopatologico nell’ambito delle malattie cardiovascolari e ci sono prove che mostrano il ruolo del sistema apelinergico nella regolazione della pressione sanguigna in vitro e in modelli animali. Il ruolo di apelina-APJ nella fisiologia del sistema cardiovascolare e la sua interazione con altri processi neuroendocrini non è stato completamente chiarito. Tuttavia, gli studi riportati indicano che la trasmissione del segnale mediata da apelina possa essere coinvolta nella regolazione della pressione arteriosa, funzione contrattile cardiaca, bilancio idrico, l’angiogenesi e l’inibizione dell’apoptosi. Abbiamo valutato la possibile relazione tra i polimorfismi G212A e A445C di APJ e la presenza di malattia coronarica (CAD) in pazienti italiani e nei controlli sani mediante RFLP-PCR. Abbiamo analizzato le frequenze alleliche e genotipiche dei polimorfismi APJ in 664 pazienti (378 con ipertensione) e 143 controlli. Non c’erano differenze tra le frequenze alleliche e genotipiche nei pazienti rispetto ai controlli per entrambi i polimorfismi analizzati. Nella popolazione CAD abbiamo osservato un aumento della frequenza dell’allele G212 nei pazienti con ipertensione rispetto ai pazienti senza ipertensione. Nessuna differenza è stata invece evidenziata nei due sottogruppi per il polimorfismo A445C. Anche se il ruolo funzionale del polimorfismo G212A non è stato ancora identificato, è possibile ipotizzare che la presenza dell’allele A sia in grado di causare un aumento nella funzione del sistema apelina/APJ associato ad un minor rischio di ipertensione arteriosa (IA)

Role of cardiac magnetic resonance in the differential diagnosis between arrhythmogenic cardiomyopathy with left ventricular involvement and previous infectious myocarditis

Aims: Arrhythmogenic cardiomyopathy with left ventricular involvement (ACM-LV), particularly in case of isolated left ventricular involvement (i.e. left dominant arrhythmogenic cardiomyopathy, LDAC) and previous infectious myocarditis (pIM) may have overlapping clinical and cardiac magnetic resonance (CMR) features. To date, there are no validated CMR criteria for the differential diagnosis between these conditions. The present study aimed to identify CMR characteristics to distinguish ACM-LV from pIM. Methods and results: This observational, retrospective, single-centre study included 30 pIM patients and 30 ACM-LV patients. In ACM-LV patients CMR was performed at diagnosis; in patients with pIM, CMR was performed six months after acute infection. CMR analysis included quantitative assessment of left ventricle (LV) volumes, systolic function and wall thicknesses, qualitative and quantitative assessment of late gadolinium enhancement (LGE) sequences. Compared with pIM, ACM-LV patients showed slightly larger LV volumes, more frequent regional wall motion anomalies and reduced wall thicknesses. ACM-LV patients had higher amounts of LV LGE and extension. Notably, the LDAC subgroup had the highest amount of LV LGE. LV LGE amount > 15 g and a LV LGE percentage > 30% of LV mass discriminated ACM-LV from pIM with a 100% specificity. LGE segmental distribution was superimposable among the groups, except for septal segments that were more frequently involved in ACM-LV and LDAC patients. Conclusions: A great extension of LV LGE (a cut-off of LGE >15 g and a percentage above 30% of LV LGE in relation to total myocardial mass) discriminates ACM-LV from pIM with extremely high specificity

Novel and recurrent mutations in the NF1 gene in Italian patients with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders in humans, affecting 1 in 3500 individuals. NF1 is a fully penetrant exhibiting a mutation rate some 10-fold higher compared to most other disease genes. As a consequence, a high number of cases (up to 50%) are sporadic. Mutation detection is complex due to the large size of NF1 gene, the presence of pseudogenes and the great variety of lesions. In the present study we attempted to delineate the NF1 mutational spectrum in the Italian population reporting four-year experience with the direct analysis of the whole NF1 coding region in 110 unrelated subjects affected by NF1. For each patient, the whole coding sequence and all splice sites were studied for mutations, either by the protein truncation test (PTT), or, most often, by denaturing high performance liquid chromatography (DHPLC). Mutations were identified in 75 (68%) patients. Twenty-two mutations were found to be novel. The detection rate for the different methods was 7/18 (39%) for PTT, and 68/103 (66%) for DHPLC. The mutations were evenly distributed along the NF1 coding sequence. Thirty-two of the 75 unrelated NF1 patients in which germline mutations were identified (32/75, 43%) harbour 23 different recurrent mutations. Fifteen sequence variants likely to represent non-pathogenic polymorphisms were observed at the NF1 locus. Genotype-phenotype analysis was unable to detect any obvious correlation. Copyright 2004 Wiley-Liss, Inc