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Menzaghi C.,Research Unit of Diabetes and Endocrine Diseases | Salvemini L.,Research Unit of Diabetes and Endocrine Diseases | Paroni G.,Research Unit of Diabetes and Endocrine Diseases | De Bonis C.,Research Unit of Diabetes and Endocrine Diseases | And 8 more authors.
Journal of Internal Medicine | Year: 2010

Menzaghi C, Salvemini L, Paroni G, De Bonis C, Mangiacotti D, Fini G, Doria A, Di Paola R, Trischitta V (IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy, Joslin Diabetes Center and Harvard Medical School, Boston, MA, USA, "Sapienza" University; IRCCS Casa Sollievo della Sofferenza-Mendel Institute, Rome, Italy). Circulating HMW adiponectin isoform is heritable and shares a common genetic background with insulin resistance in nondiabetic White Caucasians from Italy: evidence from a family-based study. J Intern Med 2010; 267: 287-294. Objective. Reduced circulating adiponectin levels contribute to the aetiology of insulin resistance. Adiponectin circulates in three different isoforms: high molecular weight (HMW), medium molecular weight (MMW) and low molecular weight (LMW) isoforms. The genetics of adiponectin isoforms is mostly unknown. Our aim was to investigate whether and to which extent circulating adiponectin isoforms are heritable and whether they share common genetic backgrounds with insulin resistance-related traits. Methods. In a family-based sample of 640 nondiabetic White Caucasians from Italy, serum adiponectin isoforms concentrations were measured by ELISA. Three single nucleotide polymorphisms (SNPs) in the ADIPOQ gene previously reported to affect total adiponectin levels (rs17300539, rs1501299 and rs677395) were genotyped. The heritability of adiponectin isoform levels was assessed by variance component analysis. A linear mixed effects model was used to test the association between SNPs and adiponectin isoforms. Bivariate analyses were conducted to study genetic correlations between adiponectin isoforms levels and other insulin resistance-related traits. Results. All isoforms were highly heritable (h 2 = 0.60-0.80, P = 1.0 × 10 -13-1.0 × 10 -23). SNPs rs17300539, rs1501299 and rs6773957 explained a significant proportion of HMW variance (2-9%, P = 1.0 × 10 -3-1.0 × 10 -5). In a multiple-SNP model, only rs17300539 and rs1501299 remained associated with HMW adiponectin (P = 3.0 × 10 -4 and 2.0 × 10 -2). Significant genetic correlations (P = 1.0 × 10 -2-1.0 × 10 -5) were observed between HMW adiponectin and fasting insulin, homeostasis model assessment of insulin resistance, HDL cholesterol and the metabolic syndrome score. Only rs1501299 partly accounted for these genetic correlations. Conclusion. Circulating levels of adiponectin isoforms are highly heritable. The genetic control of HMW adiponectin is shared in part with insulin resistance-related traits and involves, but is not limited to, the ADIPOQ locus. © 2009 Blackwell Publishing Ltd. Source

Spoto B.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Testa A.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Parlongo R.M.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | Tripepi G.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy | And 3 more authors.
Nephrology Dialysis Transplantation | Year: 2012

Background. Left ventricular hypertrophy (LVH) and insulin resistance (IR) are frequent complications of end-stage renal disease (ESRD). The ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) gene, whose variability has been repeatedly associated with IR, codes for a membrane glycoprotein which inhibits insulin-receptor signalling. Methods. We investigated the relationship of ENPP1 variability, as indicated by 10 single nucleotide polymorphisms (SNPs) representative of the gene haploblock structure, with left ventricular mass and geometry (by echocardiography) in an ethnically homogeneous series of 238 Caucasian ESRD patients. Results. ENPP1 rs1974201 and rs9402349 polymorphisms were coherently associated (P ranging from 0.04 to 0.005) with indicators of left ventricular (LV) myocardial hypertrophy (mean wall thickness) and concentric remodelling (relative wall thickness and LV mass-to-volume ratio) but unrelated with the cavitary component of the LV (left ventricular end-diastolic volume). As compared to individuals carrying the alternative genotypes, the risk of LV concentric remodelling was approximately doubled in major allele homozygous for rs1974201 [odds ratio (OR) of GG versus GC + CC: 2.31, 95% confidence interval (CI): 1.30-4.12, P = 0.004] and rs9402349 (OR of AA versus AC + CC: 1.91, 95% CI: 1.02-3.56, P = 0.04) polymorphisms.Conclusions.Coherent associations exists between echocardiographic parameters of LV myocardial hypertrophy and concentric remodelling and ENPP1 variability in ESRD patients. These data support the hypothesis that IR is a relevant factor in the pathogenesis of myocardiopathy in this population. © 2011 The Author. Source

Prudente S.,IRCCS Casa Sollievo della Sofferenza Mendel Institute | Baratta R.,University of Catania | Andreozzi F.,University of Catanzaro | Morini E.,IRCCS Casa Sollievo della Sofferenza Mendel Institute | And 14 more authors.
Diabetologia | Year: 2010

Aims/hypothesis The results of studies on the genetics of complex traits need to be replicated and to reach robust statistical significance before they can be considered as established. We here tried to replicate the previously reported association between the TRIB3 Q84R polymorphism (rs2295490) and glucose homeostasis. Methods Three samples of Europeans with fasting glucose <7.0 mmol/l were studied. In sample 1 (n=791), the association between TRIB3 Q84R and impaired glucose regulation (IGR; defined as impaired fasting glucose and/or impaired glucose tolerance and/or type 2 diabetes by OGTT) and insulin sensitivity (ISI), and its interplay with early-phase insulin secretion (i.e. disposition index [DI]) were analysed. Sample 2 (n=374) and sample 3 (n=394) were used to replicate the association with IGR and insulin sensitivity (by glucose clamp), respectively. Genotyping was performed by TaqMan allele discrimination. Results R84 carriers were at higher risk of IGR: OR for the additive model 1.54, p=0.004, and 1.63, p=0.027, in samples 1 and 2, respectively. In sample 1, both ISI (p=0.005) and DI (p=0.043) were progressively lower from QQ to QR and RR individuals. A 'triangulation approach' indicated that the association with IGR was mostly mediated by DI rather than by ISI changes (i.e. being the expected ORs 1.51 and 1.25, respectively). In sample 3, glucose disposal was 38.8±17.7, 33.8±14.4, and 31.6±13.3 μmol min-1kg-1, p=0.022, in QQ, QR and RR individuals, respectively. Conclusions/interpretation Our data confirm that the TRIB3 R84 variant affects glucose homeostasis and suggest this effect is due to an alteration of the interplay between insulin sensitivity and secretion. © Springer-Verlag 2010. Source

De Cosmo S.,Unit of Endocrinology | Prudente S.,IRCCS Casa Sollievo della Sofferenza Mendel Institute | Lamacchia O.,University of Foggia | Lapice E.,University of Naples Federico II | And 13 more authors.
Nephrology Dialysis Transplantation | Year: 2011

Background. Insulin resistance has a role in diabetic nephropathy. The A12 variant of the PPARγ2 P121A polymorphism has been firmly associated with reduced risk of insulin resistance, while its role on the risk of albuminuria in patients with type 2 diabetes is uncertain. This study investigated whether the PPARγ2 P12A polymorphism modulates the risk of albuminuria in these patients. Methods. We tested the association between the A12 variant and albuminuria in three new case-control studies in diabetic patients from Italy (n = 841, n = 623 and n = 714 patients, respectively) and then performed a meta-analysis of all studies available to date. The nine studies we meta-analysed (six previously published and three presented here) comprised a total of 2376 cases and 4188 controls. Results. In none of the three new studies was a significant association observed with odds ratio (OR) [95% confidence intervals (95% CI)] being 1.115, 0.799 and 0.849 (P = 0.603, 0.358 and 0.518, respectively). At meta-analysis, the overall OR (95% CI) for association between A12 and albuminuria was 0.694 (0.528-0.912). A significant heterogeneity of the genetic effect was observed (P = 0.026), which was totally explained by the different method of urine collection and albuminuria definition utilized across the studies. In fact, most of the effect was observed in the four studies determining albumin excretion rate rather than in those using albumin concentration in a single spot (OR, 95% CI: 0.529, 0.397-0.706, P = 0.0000164 and 0.919, 0.733-1.153, P = 0.47, respectively).Conclusion. The present study shows that the PPARγ2 Ala12 variant is significantly associated with a reduced risk of albuminuria among patients with type 2 diabetes. © 2011 The Author. Source

Mazza T.,IRCCS Casa Sollievo della Sofferenza Mendel Institute | Castellana S.,IRCCS Casa Sollievo della Sofferenza Mendel Institute
Algorithms | Year: 2013

Data storage is a major and growing part of IT budgets for research since many years. Especially in biology, the amount of raw data products is growing continuously, and the advent of the so-called "next-generation" sequencers has made things worse. Affordable prices have pushed scientists to massively sequence whole genomes and to screen large cohort of patients, thereby producing tons of data as a side effect. The need for maximally fitting data into the available storage volumes has encouraged and welcomed new compression algorithms and tools. We focus here on state-of-the-art compression tools and measure their compression performance on ABI SOLiD data. © 2013 by the authors; licensee MDPI, Basel, Switzerland. Source

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