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Maria Stella Graziani

Deputy Director
Martina Zaninotto

Associate Editors
Ferruccio Ceriotti
Davide Giavarina
Bruna Lo Sasso
Giampaolo Merlini
Martina Montagnana
Andrea Mosca
Paola Pezzati
Rossella Tomaiuolo
Matteo Vidali

EIC Assistant
Francesco Busardò

International Advisory Board Khosrow Adeli Canada
Sergio Bernardini Italy
Marcello Ciaccio Italy
Eleftherios Diamandis Canada
Philippe Gillery France
Kjell Grankvist Sweden
Hans Jacobs The Netherlands
Eric Kilpatrick UK
Magdalena Krintus Poland
Giuseppe Lippi Italy
Mario Plebani Italy
Sverre Sandberg Norway
Ana-Maria Simundic Croatia
Tommaso Trenti Italy
Cas Weykamp The Netherlands
Maria Willrich USA
Paul Yip Canada

Biomedia srl
Via L. Temolo 4, 20126 Milano

Responsible Editor
Giuseppe Agosta

Editorial Secretary
Chiara Riva
Biomedia srl
Via L. Temolo 4, 20126 Milano
Tel. 0245498282


ISSN print: 0393 – 0564
ISSN digital: 0392- 7091

BC: Articoli scritti da F. Zarrilli

Suicidio tra umanesimo e scienza
Suicide between humanism and science
<p>Suicide is among the first 10 causes of death in industrialized countries,&nbsp;even if its incidence is declining. Familiarity frequently occurs in suicide and a myriad of polymorphisms in candidate&nbsp;genes has been studied as risk factors. Among these, genes encoding enzymes, transporters or receptors of the&nbsp;serotoninergic and dopaminergic systems have been widely studied with conflicting results. Also the metabolism of&nbsp;cholesterol (and serum cholesterol concentrations) seems to have a role in the pathogenesis of suicide. In the last&nbsp;years, our group contributed to study brain derived neurotrophic factor (BDNF) and its TrkB receptor genes in the&nbsp;DNA from Wernicke area from a large cohort of suicide subjects and controls. In particular, we excluded that the<br />expression of BDNF and its receptor may be modulated by gene mutations. However, the levels of BDNF gene<br />expression were significantly lower in the brain tissue from suicide subjects. We demonstrated that the altered BDNF&nbsp;expression was due to the enhanced methylation of BDNF promoter. These studies first revealed the association&nbsp;between epigenetics and suicide suggesting a novel model of interaction between environment and genes in the&nbsp;pathogenesis of suicide.</p>
Biochimica Clinica ; 38(2) 121-128
Opinioni - Opinions
Emofilia, come si concluderà la storia?
Hemophilia, how will end the story?
<p>Hemophilia A (HA) and B (HB) are the most frequent inherited bleeding&nbsp;disorders caused by defects in the F8C and F9 genes that encode coagulation factor VIII and factor IX, respectively.&nbsp;Both HA and HB are X-linked recessive diseases and have an incidence of 1:5000 and 1:30,000 males, respectively.&nbsp;The diagnosis is based on normal prothrombin time, altered activated partial thromboplastin time and reduced activity<br />of factor VIII or factor IX in plasma. Furthermore, laboratory contributes to identify the inhibitor (an immunoglobulin&nbsp;against the factor that some hemophilic patients develop during therapy) and to reveal acquired hemophilia. Carrier&nbsp;females of HA and HB are tipically asymptomatic and can be identified only by molecular analysis; their evaluation is&nbsp;important, as one third of cases of hemophilia is due to novel mutations and in these cases the mother (and&nbsp;consanguineous females) of the proband have no risk to be carrier. Both diseases are due to a myriad of different&nbsp;mutations (mostly private), so that the molecular diagnosis is based on scanning techniques or gene sequencing.&nbsp;Given the number of hemophilic patients that experience severe perinatal complications, high-risk couples usually&nbsp;require prenatal diagnosis. We revise here our experience on 50 prenatal diagnoses of hemophilia. The clinical&nbsp;heterogeneity of hemophilic patients prompted many groups to study prothrombotic gene variants in these subjects&nbsp;to investigate whether such variants modify the clinical expression of disease. Finally, therapy (using recombinant&nbsp;factors) and, in a near future, gene therapy will change the natural history of hemophilic patients.</p>
Biochimica Clinica ; 37(6) 454-460
Rassegne - Reviews
Identificazione e caratterizzazione di mutazioni in regioni regolatorie del gene malattia della fibrosi cistica
Identification and characterization of mutations in regulatory regions of cystic fibrosis disease gene
<p>Mutation&nbsp;epidemiology is crucial for cystic fibrosis (CF) diagnosis and counselling. ~6%-7% of alleles from CF patients do not bear&nbsp;mutations in the coding regions of the Cystic Fibrosis Transmembrane Regulator (CFTR) disease gene. In these&nbsp;patients, mutations may be present in non-coding, regulatory regions of the gene as i) intronic regions (particularly in&nbsp;high conserved sequences), ii) the promoter region or iii) the area at the 3&rsquo; of the gene, which is the target of microRNA&nbsp;regulation. We studied these regions by gene sequencing in a group of CF patients with one or both unidentified&nbsp;mutations after the analysis of CFTR coding regions, and in a group of CF patients with a different clinical expression of&nbsp;disease to evaluate if mutations in such regions may have a role in modulating CF clinical expression. Our analysis&nbsp;revealed: i) a dozen of mutations (most novel) in the large promoter area of 6000 bp at the 5&rsquo; of the gene; expression&nbsp;studies in four cell lines demonstrated that a half of such mutations may have a pathogenic effect; ii) a series of mutations&nbsp;in 52 conserved sequence tags (CSTs), i.e. intronic regions with a high homology between humans and mouse;&nbsp;expression studies revealed the pathogenic effect of one of these mutations; iii) finally, three mutations in the 1500 bp&nbsp;region at the 3&rsquo; of the gene; one of this has a pathogenic role, enhancing the interaction of CFTR with two inhibitory&nbsp;microRNAs. To the best of our knowledge, this is the first example of such pathogenic mechanism in a monogenic&nbsp;disorder. On the contrary, no mutations were identified in patients with different clinical expression in any of the three<br />non-coding regions. To conclude, the sequencing of non coding regions may improve the detection rate of molecular&nbsp;analysis in CF, but functional studies are required to define the pathogenic effect of novel mutations.</p>
Biochimica Clinica ; 37(6) 465-469
Contributi scientifici - Scientific papers
Polimorfismo I/D del gene per l’enzima di conversione dell’angiotensina (ACE): gene della longevità o fattore di rischio nella patologia ipertensiva?
Polymorphism of the angiotensin converting enzyme gene: longevity gene or risk factor in hypertensive disease?
<p>In recent decades, the increase in life expectancy stimulated the study of aging processes and the search for&nbsp;candidate genes involved in longevity. The angiotensin converting enzyme (ACE), present in all endothelial cells, plays&nbsp;an essential role in maintaining the homeostasis of blood flow by regulating the production of the vasoconstrictor&nbsp;angiotensin II and inactivating the bradykinin. Some studies reported a possible association between the polymorphism&nbsp;I/D of ACE gene and either hypertension and longevity. The present study was aimed to confirm these data. We studied&nbsp;two large cohorts of nonagenarians and centenarians. One was from Sardinia (200 subjects, 88 males, mean age: 96&nbsp;years) and their data were compared to a group of 222 subjects (106 males, mean age: 44 years) from the general&nbsp;population of the same geographic area. The latter group of longeve subjects (161 subjects, 71 males, mean age: 97&nbsp;years) was from Southern Italy. Furthermore, we studied 146 hypertensive patients (98 males, mean age: 51 years) and&nbsp;172 normotensive subjects (86 males, mean age: 33 years) from Southern Italy. The ACE I/D polymorphism was typed&nbsp;by polymerase chain reaction; the amplified 490 bp (allele I) and 190 bp (allele D) were visualized on 2% agarose gel.&nbsp;Hypertensive subjects had a significantly different distribution of ACE genotypes as compared to normotensive ones&nbsp;(P=0.001) and a higher frequency of the D/D genotype. Long-lived subjects from Sardinia showed a significantly different&nbsp;distribution of ACE genotypes as compared to subjects from the general population of the same geographic area (P&nbsp;&lt;0.001), to long-lived subjects from Southern Italy (P &lt;0.001), to hypertensive patients (P=0.011) and to normotensive&nbsp;subjects from Southern Italy (P &lt;0.001). Surprisingly, they had the highest frequency of the D/D genotype among the&nbsp;compared groups. Our study indicates that: i) centenarians of different ethnic origin have a different genetic background,&nbsp;ii) there is a possible association between longevity and allelic variants of ACE, even if only in specific ethnic groups (i.e.,&nbsp;Sardinian) and iii) ACE polymorphisms are a predisposing factor to hypertension.</p>
Biochimica Clinica ; 37(6) 461-464
Contributi scientifici - Scientific papers