Publications by authors named "Giuseppe Miscio"

16 Publications

  • Page 1 of 1

Diagnosis of COVID-19 in Patients with Negative Nasopharyngeal Swabs: Reliability of Radiological and Clinical Diagnosis and Accuracy Versus Serology.

Diagnostics (Basel) 2021 Feb 25;11(3). Epub 2021 Feb 25.

Unit of Internal Medicine, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

Background: The diagnosis of Coronavirus disease 2019 (COVID-19) relies on the positivity of nasopharyngeal swab. However, a significant percentage of symptomatic patients may test negative. We evaluated the reliability of COVID-19 diagnosis made by radiologists and clinicians and its accuracy versus serology in a sample of patients hospitalized for suspected COVID-19 with multiple negative swabs.

Methods: Admission chest CT-scans and clinical records of swab-negative patients, treated according to the COVID-19 protocol or deceased during hospitalization, were retrospectively evaluated by two radiologists and two clinicians, respectively.

Results: Of 254 patients, 169 swab-confirmed cases and one patient without chest CT-scan were excluded. A total of 84 patients were eligible for the reliability study. Of these, 21 patients died during hospitalization; the remaining 63 underwent serological testing and were eligible for the accuracy evaluation. Of the 63, 26 patients showed anti-Sars-Cov-2 antibodies, while 37 did not. The inter-rater agreement was "substantial" (kappa 0.683) between radiologists, "moderate" (kappa 0.454) between clinicians, and only "fair" (kappa 0.341) between radiologists and clinicians. Both radiologic and clinical evaluations showed good accuracy compared to serology.

Conclusions: The radiologic and clinical diagnosis of COVID-19 for swab-negative patients proved to be sufficiently reliable and accurate to allow a diagnosis of COVID-19, which needs to be confirmed by serology and follow-up.
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http://dx.doi.org/10.3390/diagnostics11030386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996330PMC
February 2021

False-positive results of SARS-CoV-2 IgM/IgG antibody tests in sera stored before the 2020 pandemic in Italy.

Int J Infect Dis 2021 Mar 28;104:159-163. Epub 2020 Dec 28.

Immunohematology and Transfusion Medicine Service, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.

Objectives: Aside from the outbreak of the coronavirus disease 2019 (COVID-19), serological tests are not well known for their diagnostic value. We assessed the performance of serological tests using stored sera from patients with a variety of pathologic conditions, collected before the 2020 pandemic in Italy.

Methods: Rapid lateral flow tests and Enzyme-Linked Immunosorbent Assays (ELISA) that detect Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were carried out using 1150 stored human serum samples that had been collected in 2018 and 2019. The tests were also run using samples from 15 control patients who had positive or negative oral swab test results, as assessed using real-time reverse transcription-polymerase chain reaction (rRT-PCR). The urea dissociation test was employed to rule out false-positive reactivity in the two antibody detection methods.

Results: The lateral flow tests revealed 21 positive samples from the stored sera: 12 for IgM, four for IgG, and five for IgM/IgG. Among the nine rRT-PCR- positive controls, six individuals presented IgG and three IgM/IgG positivity. Using the urea (6 mol/L) dissociation test, two of the twelve stored samples that had shown IgM positivity were confirmed to be positive. The ELISA test detected four IgM-positive and three IgG-positive specimens. After treatment with 4 mol/L urea, the IgM-positive samples became negative, whereas the IgG positivity persisted. All of the rRT-PCR-positive controls were found to retain IgM or IgG positivity following the urea treatment.

Conclusions: Our findings highlight the limited utility of serological testing for the SARS-CoV-2 virus based on the results of specimens collected before the outbreak of the infection.
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http://dx.doi.org/10.1016/j.ijid.2020.12.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834192PMC
March 2021

Reduction of ADAMTS13 Levels Predicts Mortality in SARS-CoV-2 Patients.

TH Open 2020 Jul 30;4(3):e203-e206. Epub 2020 Aug 30.

Research Unit of Thrombosis and Hemostasis, Fondazione IRCCS "Casa Sollievo della Sofferenza," San Giovanni Rotondo, Italy.

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http://dx.doi.org/10.1055/s-0040-1716379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456602PMC
July 2020

Pharmacogenetics in the clinical analysis laboratory: clinical practice, research, and drug development pipeline.

Expert Opin Drug Metab Toxicol 2019 Sep 12;15(9):751-765. Epub 2019 Sep 12.

Research Laboratory, Complex Structure of Geriatrics, Department of Medical Sciences, Fondazione IRCCS Casa Sollievo della Sofferenza , Foggia , Italy.

: Over the last decade, the spread of next-generation sequencing technology along with the rising cost in health management in national health systems has led to widespread use/abuse of pharmacogenetic tests (PGx) in the practice of many clinical disciplines. However, given their clinical significance, it is important to standardize these tests for having an interaction with the clinical analysis laboratory (CAL), in which a PGx service can meet these requirements. : A diagnostic test must meet the criteria of reproducibility and validity for its utility in the clinical routine. This present review mainly describes the utility of introducing PGx tests in the CAL routine to produce correct results useful for setting up personalized drug treatments. : With a PGx service, CALs can provide the right tool to help clinicians to make better choices about different categories of drugs and their dosage and to manage the economic impact both in hospital-based settings and in National Health Services, throughout electronic health records. Advances in PGx also allow a new approach for pharmaceutical companies in order to improve drug development and clinical trials. As a result, CALs can achieve a powerful source of epidemiological, clinical, and research findings from PGx tests.
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http://dx.doi.org/10.1080/17425255.2019.1658742DOI Listing
September 2019

CYP2D6 genotypes in revolving door patients with bipolar disorders: A case series.

Medicine (Baltimore) 2018 Sep;97(37):e11998

Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Foggia Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari "Aldo Moro", Bari Laboratory of Clinical Chemistry, Department of Clinical Pathology, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo Psychiatric Unit, Department of Clinical and Experimental Medicine, University of Foggia, Foggia Institute of Neurology, Catholic University of Sacred Heart, Rome Department of Clinical Research in Neurology, Neurodegenerative Disease Unit, University of Bari "Aldo Moro", Azienda Ospedaliera "Card. G. Panico", Tricase, Lecce, Italy.

Rationale: In psychiatric disorders, interindividual differences in cytochrome P450 (CYP)2D6 (CYP2D6) enzymatic activity could be responsible of adverse drug reactions (ADRs) and therapeutic failures (TFs) for CYP2D6-metabolized drugs, contributing to the periodical hospital readmissions of the revolving door (RD) condition.

Patient Concerns: We investigated CYP2D6 genotypes in a controlled series of 5 consecutive RD patients with Bipolar Disorder (BD).

Diagnoses: Psychiatric patients affected by Bipolar Disorder.

Interventions: We defined TFs as a difference at the Brief Psychiatric Rating Scale score ΔBPRS < 25% at each 1-week of stable treatment, and ADRs as the onset of extrapyramidal symptoms and/or metabolic impairment with weight gain.

Outcomes: At 3 months, a mean number of 2.75 ± 1.26 ADR and a mean ΔBPRS score of 16.07 ± 0.05% were observed. At 6 months of follow-up, compared to the only patient without BD (ΔBPRS < 32.10%), BD patients (n = 4) showed TFs (ΔBPRS < 25%). CYP2D6 genotyping revealed intermediate metabolizer phenotypes for BD patients and an extensive metabolizer phenotype for the patient without BD. In BD patients, the ratio of drugs maintained/discontinued for TFs or ADRs was 1.75 for non-CYP2D6 versus 0.33 for CYP2D6 interacting drugs, while the proportion of ADR:TF was 0:4 versus 6:3.

Lessons: Our findings may suggest that CYP2D6 clinically relevant genotypes may be involved in the unwanted outcomes observed in RD patients with BD.
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http://dx.doi.org/10.1097/MD.0000000000011998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155952PMC
September 2018

Pharmacogenetics of neurological and psychiatric diseases at older age: has the time come?

Expert Opin Drug Metab Toxicol 2017 Mar 20;13(3):259-277. Epub 2016 Oct 20.

c Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences , IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo , Italy.

Introduction: In recent years, a number of pharmacological approaches for treating neuropsychiatric conditions at older age have proven to be inadequate. The resulting increased prevalence of therapeutic failures (TF) and a worsening of clinical symptoms often linked to adverse reactions (ADRs), are perhaps among the major causes of the increasing rate of hospitalizations and institutionalizations observed in these patients. Areas covered: This review underlines the importance of pharmacogenetic data to fingerprint the pharmacological treatment of neuropsychiatric late-life conditions throughout the analysis of metabolizing enzymes and transporters of psychotropic drugs, mainly those of the cytochrome P450 (CYP) family. Pharmacodynamic response measures as treatment effects mediated through targets (i.e., receptors in the brain) may also contribute to this image. Expert opinion: CYP genetics is the basis of a continuum on which environmental and physiological factors act, modeling the phenotype observed in clinical practice with advancing age. Furthermore, other specific polymorphic genes influence drug response through differential effects of their functional genetic variants. The known genotypes associated with an altered metabolizer status and drug transporters may help clinical decision-making to avoid concomitant treatments, reduce therapeutic attempts and increase drug safety in neuropsychiatric conditions in older age, after controlling for other clinical variables.
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http://dx.doi.org/10.1080/17425255.2017.1246533DOI Listing
March 2017

The circadecadal rhythm of oscillation of umbilical cord blood parameters correlates with geomagnetic activity - An analysis of long-term measurements (1999-2011).

Chronobiol Int 2016 13;33(9):1136-1147. Epub 2016 Jul 13.

f Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit , IRCCS "Casa Sollievo della Sofferenza" , S. Giovanni Rotondo (FG) , Italy.

Recently, we have shown that the contents of total nucleated cells (TNCs) and CD34 hematopoietic stem and progenitor cells (CD34 HSPCs) as well as the cord blood volume (CBV) in umbilical cord blood (UCB) show a circadecadal (~10 years) rhythm of oscillation. This observation was based on an analysis of 17,936 cord blood donations collected during 1999-2011. The aim of the present study was to investigate whether this circadecadal rhythm of oscillation in TNCs, CD34 HSPCs and CBV is related to geomagnetic activity. For the analysis, the yearly averages of TNCs, CD34 HSPCs and CBV in UCB were correlated with geomagnetic activity (Dcx index). Our analysis revealed that (i) all three UCB parameters were statistically significantly correlated with the level of geomagnetic activity, (ii) CBV showed a linear correlation with the Dcx index (r = 0.5290), (iii) the number of TNCs and CD34 HSPCs were quadratic inversely correlated with the Dcx index (r = -0.5343 and r = -0.7749, respectively). Furthermore, (iv) CBV and the number of TNCs were not statistically significantly correlated with the number of either modest or intense geomagnetic storms per year, but (v) the number of CD34 HSPCs was statistically significantly correlated with the number of modest (r = 0.9253) as well as intense (r = 0.8683) geomagnetic storms per year. In conclusion, our study suggests that UCB parameters correlate with the state of the geomagnetic field (GMF) modulated by solar activity. Possible biophysical mechanisms underlying this observation, as well as the outcome of these findings, are discussed.
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http://dx.doi.org/10.1080/07420528.2016.1202264DOI Listing
January 2018

Time related variations in stem cell harvesting of umbilical cord blood.

Sci Rep 2016 Feb 24;6:21404. Epub 2016 Feb 24.

Interinstitutional Department for Continuity of Care of Empoli, School of Medicine, University of Florence, Florence, Italy.

Umbilical cord blood (UCB) contains hematopoietic stem cells and multipotent mesenchymal cells useful for treatment in malignant/nonmalignant hematologic-immunologic diseases and regenerative medicine. Transplantation outcome is correlated with cord blood volume (CBV), number of total nucleated cells (TNC), CD34+ progenitor cells and colony forming units in UCB donations. Several studies have addressed the role of maternal/neonatal factors associated with the hematopoietic reconstruction potential of UCB, including: gestational age, maternal parity, newborn sex and birth weight, placental weight, labor duration and mode of delivery. Few data exist regarding as to how time influences UCB collection and banking patterns. We retrospectively analyzed 17.936 cord blood donations collected from 1999 to 2011 from Tuscany and Apulia Cord Blood Banks. Results from generalized multivariable linear mixed models showed that CBV, TNC and CD34+ cell were associated with known obstetric and neonatal parameters and showed rhythmic patterns in different time domains and frequency ranges. The present findings confirm that volume, total nucleated cells and stem cells of the UCB donations are hallmarked by rhythmic patterns in different time domains and frequency ranges and suggest that temporal rhythms in addition to known obstetric and neonatal parameters influence CBV, TNC and CD34+ cell content in UBC units.
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http://dx.doi.org/10.1038/srep21404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764902PMC
February 2016

Four phases of checks for exclusion of umbilical cord blood donors.

Blood Transfus 2011 Jul 7;9(3):286-91. Epub 2011 Apr 7.

Obstetrics and Gynaecology Unit, Di Venere Hospital, Bari, Italy.

Aim: The aim of this study was to analyse umbilical cord blood (UCB) collection over 1 year between October 2008 and September 2009, seeking ways to improve the number of suitable banked UCB units. Four phases of the process were investigated, from the consent form to the banking procedure, paying attention to the discarded UCB units.

Material And Methods: We recruited couples at 35 weeks of gestation and took an accurate history, focusing on genetic, immunological and infectious diseases. We collected UCB from pregnant women who delivered vaginally or by Caesarean section between the 37-41(+6) weeks of gestation. Some units were discarded on the basis of the patients' history, obstetric events or biological criteria. In utero collection was the preferred method of collection.

Results: During the study period, between October 2008 and September 2009, there were 1,477 deliveries in our unit. The number of couples interested in UCB donation was 595 (40.2%-595/1,477). We collected 393 UBC units. We excluded 122 patients at the phase of the history taking, counselling and informed consent (first phase check). Of the 393 units collected, 162 (41.3%) were banked whereas 231 (58.7%) were discarded because they did not fulfil biological criteria (third phase check). The volume of UCB units collected after Caesarean section was greater than the volume of units collected after vaginal delivery (95.4 mL versus 85.0 mL, respectively; p <0.01). The UCB units collected after vaginal delivery contained a higher number of total nucleated cells compared to the units collected after Caesarean section (970x10(6) cells versus 874x10(6) cells, respectively; p=0.037). None of the banked UCB units was discarded at the clinical check 6 months after delivery (fourth phase check).

Conclusions: Our study shows that strict observance of each of the checks and the collection strategy is important to guarantee the safety of the UCB units and to maximise the cost-benefit ratio. After the appropriate checks we banked UCB units from only 27.2% (162/595) of the couples who gave consent to the procedure and from only 11% (162/1,477) of all the deliveries in the 12 month study period, as 59.8% of couples were not properly informed about UCB donation.
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http://dx.doi.org/10.2450/2011.0038-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136596PMC
July 2011

The role of HSP70 on ENPP1 expression and insulin-receptor activation.

J Mol Med (Berl) 2009 Feb 16;87(2):139-144. Epub 2008 Dec 16.

Research Unit of Diabetes and Endocrine Diseases, Scientific Institute, Poliambulatorio Giovanni Paolo II, Viale Padre Pio, 71013 San Giovanni Rotondo, Italy.

Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) inhibits insulin-receptor (IR) signaling and, when over-expressed, induces insulin resistance in vitro and in vivo. Understanding the regulation of ENPP1 expression may, thus, unravel new molecular mechanisms of insulin resistance. Recent data point to a pivotal role of the ENPP1 3'UTR, in modulating ENPP1 mRNA stability and expression. We sought to identify trans-acting proteins binding the ENPP1-3'UTR and to investigate their role on ENPP1 expression and on IR signaling. By RNA electrophoresis mobility shift analysis and tandem mass spectrometry, we demonstrated the binding of heat shock protein 70 (HSP70) to ENPP1-3'UTR. Through this binding, HSP70 stabilizes ENPP1 mRNA and increases ENPP1 transcript and protein levels. This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation. Taken together these data suggest that HSP70, by affecting ENPP1 expression, may be a novel mediator of altered insulin signaling.
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http://dx.doi.org/10.1007/s00109-008-0429-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760425PMC
February 2009

Association of the Q121 variant of ENPP1 gene with decreased kidney function among patients with type 2 diabetes.

Am J Kidney Dis 2009 Feb 31;53(2):273-80. Epub 2008 Oct 31.

Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Background: Insulin resistance has a role in diabetic kidney complications. The K121Q (lysine to glutamine substitution at amino acid 121, encoded by single-nucleotide polymorphism rs1044498) variant of the ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) has been associated with insulin resistance and related vascular complications in patients with type 2 diabetes (T2D) in many, although not all, studies. This study investigated whether the ENPP1 Q121 variant modulates the risk of decreased glomerular filtration rate (GFR) in patients with T2D.

Study Design: Cross-sectional study.

Setting & Participants: 2 diabetes units from Italy (in Gargano and Padua) and 1 from the United States (Boston, MA) recruited a total of 1,392 patients with T2D.

Predictor: The ENPP1 Q121 variant.

Measurements: Estimated GFR from serum creatinine, urinary albumin excretion, blood pressure, hemoglobin A(1c), triglycerides, total cholesterol, and high-density lipoprotein cholesterol.

Outcomes: Decreased GFRs (ie, estimated GFR <60 mL/min/1.73 m(2)).

Results: In the Gargano and Boston populations, according to the dominant model of inheritance, Q121 carriers (ie, individual with either KQ or QQ alleles) had an increased risk of decreased GFR: odds ratios (ORs) of 1.69 (95% confidence interval [CI], 1.1 to 2.6) and 1.50 (95% CI, 1.0 to 2.2), respectively. In the Padua set, the association was in the same direction, but did not reach formal statistical significance (OR, 1.77; 95% CI, 0.7 to 4.5). When the 3 studies were pooled, Q121 carriers showed an increased risk of decreased GFR (OR, 1.58; 95% CI, 1.2 to 2.1; P = 0.002). Also, pooled mean differences in absolute GFRs were different across genotype groups, with Q121 carriers showing lower GFRs compared with KK individuals (P = 0.04).

Limitations: P values not approaching a genome-wide level of significance.

Conclusions: Our data suggest that patients with T2D carrying the ENPP1 Q121 variant are at increased risk of decreased GFR.
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http://dx.doi.org/10.1053/j.ajkd.2008.07.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939986PMC
February 2009

The allelic variant of LAR gene promoter -127 bp T-->A is associated with reduced risk of obesity and other features related to insulin resistance.

J Mol Med (Berl) 2004 Jul 19;82(7):459-66. Epub 2004 May 19.

Unit of Endocrinology, Scientific Institute CSS, Viale Cappuccini 1, 71013 San Giovanni Rotondo (FG), Italy.

Insulin resistance, which is pathogenic for type 2 diabetes (T2D), is under the control of largely unknown genetic determinants. LAR, a protein-tyrosine phosphatase which inhibits insulin signalling, is overexpressed in animal and human models of insulin resistance. We studied the entire sequence of the LAR gene by SSCP analysis and automatic DNA sequencing, with the aim of verifying whether its sequence variants might be associated with insulin resistance. In the 276 bp sequence upstream of the transcriptional start site (i.e. a region we have identified as having basal promoter activity) a -127 bp T-->A SNP (5% frequency) was associated with lower body mass index (BMI) ( P=0.03), waist circumference ( P=0.01), blood pressure ( P=0.01) and urinary albumin/creatinine ratio ( P=0.04) in 589 non-diabetic unrelated individuals from the Gargano region (central east coast of Italy). To quantify the risk for a high body weight conferred by the -127 T-->A SNP, the whole cohort was divided into tertiles according to the individual BMI. The risk of belonging to the heavier tertile, as compared to the leaner one, was reduced by approximately 60%. In a population from East Sicily ( n=307), T/A genotype carriers ( n=13) showed lower triglyceride levels ( P=0.04) and higher insulin sensitivity as indicated by lower plasma glucose ( P=0.03) and serum insulin ( P=0.006) during oral glucose tolerance testing (OGTT). Promoter activity, studied by cDNA transfection experiments, was similar for the A and T alleles. In conclusion, a genetic variant of the LAR gene promoter is consistently associated with features of insulin resistance in two different Caucasian populations. Although the biological relevance of this variant has yet to be determined, this finding underlines the potential importance of the LAR gene in dysregulation of insulin sensitivity and related disorders.
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http://dx.doi.org/10.1007/s00109-004-0544-1DOI Listing
July 2004

The role of PC-1 and ACE genes in diabetic nephropathy in type 1 diabetic patients: evidence for a polygenic control of kidney disease progression.

Nephrol Dial Transplant 2002 Aug;17(8):1402-7

Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza San Giovanni Rotondo (FG), Italy.

Background: The DD genotype of the ACE gene predisposes to faster diabetic nephropathy (DN) progression but its role in DN development is more controversial. We reported previously, in type 1 diabetic patients, an association between faster DN progression and the PC-1 gene Q121 variant, which associates with insulin resistance in non-diabetic subjects. We investigated here whether the combination of the ACE DD genotype and the PC-1 Q121 variant predicts the development and/or progression of DN in type 1 diabetic patients.

Methods: Type 1 diabetic patients either with (n=159) or without (n=122) nephropathy were evaluated in a cross-sectional study. DN was defined as the presence of microalbuminuria or persistent proteinuria in a subject with more than 10-year duration of disease and concomitant diabetic retinopathy, and with no evidence of heart failure or other renal disease. Seventy-five (47 male/28 female) type 1 diabetic patients with nephropathy in whom retrospective information with repeated measurements of serum creatinine was available, were analysed in a longitudinal study.

Results: No association of the PC-1 Q121 variant and the ACE D/D genotype with DN development was observed. However, the ACE DD genotype and the PC-1 Q121 variant were associated, both independently (P=0.02 and P=0.025, respectively) or in combination (P=0.02), with a faster rate of glomerular filtration rate decline. An interaction (P=0.03) was observed between the two genes in increasing the individual patient's risk of being a fast progressor.

Conclusion: Our data suggest that, in type 1 diabetic patients, the ACE and the PC-1 genes interact in increasing the individual risk of having a faster DN progression.
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http://dx.doi.org/10.1093/ndt/17.8.1402DOI Listing
August 2002

Subclinical hypothyroidism in early childhood: a frequent outcome of transient neonatal hyperthyrotropinemia.

J Clin Endocrinol Metab 2002 Jul;87(7):3209-14

Istituto di Medicina Interna, Malattie Endocrine e del Metabolismo dell'Università di Catania, Ospedale Garibaldi, 95125 Catania, Italy.

Newborns with high TSH at birth and with normal free T(4) and normal or slightly elevated TSH at the confirmatory examination are considered false positive for congenital hypothyroidism. We evaluated thyroid function, thyroid antibodies, thyroid volume and morphology, thyroperoxidase and TSH receptor genes, and auxological data in 56 false positive children at 16-44 months of age. In these children thyroid function at confirmatory examination was fully normal in 33 (TSH, 0.8-4.9 mU/liter; group I) and nearly normal (borderline elevated TSH, 5.0-11.7 mU/liter) in the other 23 (group II). Compared with 65 control children with normal TSH at birth, false positive children had significantly higher basal serum TSH (mean +/- SD, 4.38 +/- 2.2 vs. 1.4 +/- 0.8 mU/liter; P < 0.01). Subclinical hypothyroidism, indicated by increased basal TSH and/or increased TSH response to TRH, was present in 36% children in group I and 70% in group II. Free T(4) was within the normal range in all children. Compared with the control group, false positive children had significantly higher free T(3) values (4.9 +/- 0.8 vs. 3.7 +/- 1.0 pmol/liter; P < 0.01) and a higher prevalence of antithyroid antibodies (25% vs. 1.5%; P < 0.001). Frequent thyroid morphology abnormalities and frequent thyroperoxidase and TSH receptor gene sequence variations were also observed. In conclusion, newborns classified false positive at congenital hypothyroidism screening have a very high risk of subclinical hypothyroidism in infancy and early childhood.
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http://dx.doi.org/10.1210/jcem.87.7.8662DOI Listing
July 2002

A variation in 3' UTR of hPTP1B increases specific gene expression and associates with insulin resistance.

Am J Hum Genet 2002 Mar 6;70(3):806-12. Epub 2002 Feb 6.

Unit of Endocrinology, Scientific Institute CSS, San Giovanni Rotondo (FG), Italy.

Protein tyrosine phosphatase 1B (PTP1B) inhibits insulin signaling and, when overexpressed, plays a role in insulin resistance (Ahmad et al. 1997). We identified, in the 3' untranslated region of the PTP1B gene, a 1484insG variation that, in two different populations, is associated with several features of insulin resistance: among male individuals, higher values of the insulin resistance HOMA(IR) index (P=.006), serum triglycerides (P=.0002), and total/HDL cholesterol ratio (P=.025) and, among female individuals, higher blood pressure (P=.01). Similar data were also obtained in a family-based association study by use of sib pairs discordant for genotype (Gu et al. 2000). Subjects carrying the 1484insG variant showed also PTP1B mRNA overexpression in skeletal muscle (6,166 plus minus 1,879 copies/40 ng RNA vs. 2,983 plus minus 1,620; P<.01). Finally, PTP1B mRNA stability was significantly higher (P<.01) in human embryo kidney 293 cells transfected with 1484insG PTP1B, as compared with those transfected with wild-type PTP1B. Our data indicate that the 1484insG allele causes PTP1B overexpression and plays a role in insulin resistance. Therefore, individuals carrying the 1484insG variant might particularly benefit from PTP1B inhibitors, a promising new tool for treatment of insulin resistance (Kennedy and Ramachandran 2000).
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http://dx.doi.org/10.1086/339270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC384960PMC
March 2002
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