Andrea Angius

Università di Sassari, Dipartimento di Scienze Biomediche, Adjunct

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Phone: +39 0706754591
Address: Istituto di Ricerca Genetica e Biomedica (IRGB)
Cittadella Universitaria di Cagliari - 09042 Monserrato CA

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Papers by Andrea Angius

Multiple bilateral retinal astrocytic hamartomas in Usher syndrome

Journal Francais D Ophtalmologie, Mar 1, 2022

Sequencing-based GWAS on peripheral blood monocyte counts in the SardiNIA cohort

Gut microbiota composition and functional relevance in subclinical carotid atherosclerosis

Atherosclerosis, 2020

Novel <i>NALCN</i> biallelic truncating mutations in siblings with IHPRF1 syndrome

Clinical Genetics, Feb 5, 2018

Infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1) is a severe... more Infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1) is a severe autosomal recessive neurologic disorder with onset at birth or in early infancy. It is caused by mutations in the NALCN gene that encodes a voltage-independent, cation channel permeable to NM, K+ and Ca2+ and forms a channel complex with UNCSO and UNC79. So far, only 4 homozygous mutations have been found in 11 cases belonging to 4 independent consanguineous families. We studied a Sardinian family with 2 siblings presenting dysmorphic facies, hypotonia, psychomotor retardation, epilepsy, absent speech, sleep disturbance, hyperkinetic movement disorder, cachexia and chronic constipation. Polymorphic generalized seizures started at 4 and 6 years, respectively. Anti-epileptic drugs (AEDs) therapy was efficient for female proband's epilepsy, but the male still has weekly seizures. Whole exome sequencing identified 2 novel truncating mutations in NALCN allowing to assess the clinical phenotype to IHPRF1. This is the fifth family reported worldwide, and these are the first European cases with IHPRF1 syndrome with biallelic truncating mutations of NALCN.

Methylenetetrahydrofolate reductase gene polymorphisms in Burkina Faso: impact on plasma fasting homocysteine and after methionine loading test

PubMed, 2007

In Burkina Faso the levels of plasma homocysteine (Hcy) are lower and the methionine loading test... more In Burkina Faso the levels of plasma homocysteine (Hcy) are lower and the methionine loading tests suggest a more effective Hcy metabolism. The polymorphisms of methylenetetrahydrofolate reductase (MTHFR) showed a relevant difference in the allele frequencies of T MTHFR-677 in young and in old subjects, while the allele frequency of C MTHFR-1298 was comparable in young and old subjects. The aim of this paper was to study the impact of the MTHFR polymorphisms on plasma fasting Hcy and after methionine loading in Burkina Faso. The young subjects with CC MTHFR-677 genotype had levels of Hcy significantly lower than CT and TT subjects. The level of Hcy in subjects who had AA, AC and CC MTHFR-1298 genotypes were comparable. The levels of Hcy after the methionine loading test were significantly higher in CT and TT MTHFR-677 genotype. These results suggest that the genetic situation in Burkina Faso is different from that of other Western countries and this guarantees the maintenance of lower plasma levels of Hcy in young and old Africans. The elevated levels of plasma Hcy in old subjects compared to young subjects, against the low prevalence of the T allele in elderly subjects, is discussed.

There is no benefit in routinely monitoring ANCA titres in patients with granulomatosis with polyangiitis

PubMed, May 29, 2015

Objectives: To analyse the link between antineutrophil cytoplasmic antibody (ANCA) levels and ris... more Objectives: To analyse the link between antineutrophil cytoplasmic antibody (ANCA) levels and risk of relapse in patients with granulomatosis with polyangiitis (GPA), as the clinical benefit of monitoring ANCA levels is uncertain. Methods: A retrospective analysis was made of all charts available from 43 patients diagnosed with GPA, fulfilling The American College of Rheumatology 1990 criteria, and followed between 1994 and 2012 at a general internal medicine department of a university hospital. Clinical and biochemical data (i.e. anti-proteinase 3 (PR3) levels) were collected and correlated. Results: 43 relapses occurred in 25 patients (58.1% of 43 patients). When blood samples are routinely taken at a follow-up visit (i.e. low pre-test probability, ± 5.5%) in the GPA-population, a 75%-increase in the PR3-level or its reappearance has only limited positive predictive value (PPV 15.0% and 22.5% respectively) for predicting relapse. Adversely, when clinical suspicion of relapse is high (i.e. high pre-test probability, for example 50%), an increase of 75% or reappearance of PR3 makes relapse even more likely (PPV 77.5%, 81.6% respectively). Conversely, a high negative predictive value (NPV) of 99.3% and a negative likelihood ratio (LR-) of 0.12 suggest that, in the absence of PR3, relapse is unlikely if patients had detectable ANCAs at diagnosis. Conclusions: Routine ANCA monitoring in patients diagnosed with GPA has limited value. However, targeted determination of ANCA levels may be useful if a relapse is clinically suspected (i.e. high pre-test probability).

EDA2R Is Associated with Androgenetic Alopecia

Journal of Investigative Dermatology, Sep 1, 2008

Genomic history of the Sardinian population

Nature Genetics, Sep 17, 2018

The population of the Mediterranean island of Sardinia has made important contributions to genome... more The population of the Mediterranean island of Sardinia has made important contributions to genome-wide association studies of complex disease traits and, based on ancient DNA (aDNA) studies of mainland Europe, Sardinia is hypothesized to be a unique refuge for early Neolithic ancestry. To provide new insights on the genetic history of this flagship population, we analyzed 3,514 whole-genome sequenced individuals from Sardinia. We find Sardinian samples show elevated levels of shared ancestry with Basque individuals, especially samples from the more historically isolated regions of Sardinia. Our analysis also uniquely illuminates how levels of Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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Population history of the Sardinian people inferred from whole-genome sequencing

bioRxiv (Cold Spring Harbor Laboratory), Dec 7, 2016

The population of the Mediterranean island of Sardinia has made important contributions to genome... more The population of the Mediterranean island of Sardinia has made important contributions to genome-wide association studies of traits and diseases. The history of the Sardinian population has also been the focus of much research, and in recent ancient DNA (aDNA) studies, Sardinia has provided unique insight into the peopling of Europe and the spread of agriculture. In this study, we analyze whole-genome sequences of 3,514 Sardinians to address hypotheses regarding the founding of Sardinia and its relation to the peopling of Europe, including examining fine-scale substructure, population size history, and signals of admixture. We find the population of the mountainous Gennargentu region shows elevated genetic isolation with higher levels of ancestry associated with mainland Neolithic farmers and depleted ancestry associated with more recent Bronze Age Steppe migrations on the mainland. Notably, the Gennargentu region also has elevated levels of pre-Neolithic hunter-gatherer ancestry and increased affinity to Basque populations. Further, allele sharing with pre-Neolithic and Neolithic mainland populations is larger on the X chromosome compared to the autosome, providing evidence for a sex-biased demographic history in Sardinia. These results give new insight to the demography of ancestral Sardinians and help further the understanding of sharing of disease risk alleles between Sardinia and mainland populations. .

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The Changing Landscape of Naive T Cell Receptor Repertoire With Human Aging

Frontiers in Immunology, Jul 24, 2018

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Methylenetetrahydrofolate Reductase (MTHFR) from Mediterranean to Sub-Saharan Areas

Online journal of biological sciences, 2006

Complete sequence and characterization of mitochondrial and chloroplast genome of Chlorella variabilis NC64A

Mitochondrial Dna Part B, Feb 18, 2015

The complete nucleotide sequences of the mitochondrial (mtDNA) and chloroplast (cpDNA) genomes of... more The complete nucleotide sequences of the mitochondrial (mtDNA) and chloroplast (cpDNA) genomes of Chlorella variabilis NC64A (Trebouxiophyceae) have been determined in this study (GenBank accession no. KP271968 and KP271969, respectively). The mt genome assembles as a circle of 78,500 bp and contains 62 genes, including 32 protein-coding, 27 tRNA and 3 rRNA genes. The overall GC content is 28.2%, while the coding sequence is 34%. The cp genome forms a circle of 124,793 bp, containing 114 genes, including 79 protein-coding, 32 tRNA and 3 rRNA genes. The overall GC content is 33,9%, while the coding sequence is 50%.

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Sharing of mtDNA variants among 2,077 SardiNIA sequencing project participants

PLOS Genetics, Jul 14, 2015

<p>Sharing of mtDNA variants among 2,077 SardiNIA sequencing project participants.</p

Plasma chitotriosidase activity in patients with ?-thalassemia

American Journal of Hematology, Mar 21, 2003

Variable increases in chitotriosidase levels have been reported in Italian patients with ␤-thalas... more Variable increases in chitotriosidase levels have been reported in Italian patients with ␤-thalassemia major and intermedia. We measured plasma chitotriosidase levels in Israeli patients with ␤-thalassemia to ascertain its use as a universal marker of disease and/or response to therapy. Chitotriosidase levels in 39 adults (16-53 years; 30 with ␤-thalassemia major, 9 with intermedia), and in 14 children (0.7-15 years; 12 with ␤-thalassemia major, 2 with intermedia) were compared with other measures of disease, such as ferritin, hemoglobin, liver function tests, and genotype. Plasma chitotriosidase levels were normal (0.37 ± 0.04 mU/mL) in all children. Twelve adults (31%) had elevated levels (>1.33 mU/mL): 11 patients (37%) with thalassemia major and 1 patient (11%) with thalassemia intermedia. A significant correlation was only found between plasma chitotriosidase levels and ferritin levels, and with mean number of transfusions per year. The patient with the highest chitotriosidase (1,440 nmol/mL/hr) had the highest ferritin (5,175 µg/L), required the most transfusions per year (40), and had abnormal liver tests. Normal chitotriosidase levels in the pediatric cohort and increased levels in only some adults may reflect status of iron overload in macrophages; thus there may be a role for monitoring chitotriosidase in patients with ␤-thalassemia. Our results confirm results of the Italian cohort; however, in the latter, a more universal correlation was noted and chitotriosidase levels were much higher. Am.

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Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype

Scientific Reports

HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We ... more HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemotherapy (NACT). The tumoral pathological complete response (pCR) rate was 40.9%. High tumoral pCR show a scarce mortality rate vs subjects with a lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with a high percentage of infiltrating immune cells and right-sided tumors, that reduce distant metastasis and improve survival, but no incidence difference. HER2 IHC score and laterality emerge as strong predictors of tumoral pCR after NACT from machine learning analysis. HER2 IHC3+ and G3 are poor prognostic factors for HER2+ BC patients, and could be considered in the appli...

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Post GWAS analysis of a BCLA intronic region to define its role in regulating HbF levels

1 Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Citt... more 1 Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Cittadella Universitaria di Monserrato, Monserrato, CA, Italy; 2 Clinica Pediatrica 2a, Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Ospedale Regionale Microcitemie ASL8, Cagliari, Italy; 3 Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy. * These authors contributed equally to this work.

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遺伝子型推定:遺伝子型推定のための64,976のハプロタイプの参照パネル

Nature Genetics, 2016

MicroRNA-425-5p Expression Affects BRAF/RAS/MAPK Pathways In Colorectal Cancers

International Journal of Medical Sciences, 2019

Colorectal cancer (CRC) is a leading cause of cancer death worldwide and about 20% is metastatic ... more Colorectal cancer (CRC) is a leading cause of cancer death worldwide and about 20% is metastatic at diagnosis and untreatable. The anti-EGFR therapy in metastatic patients is led by the presence of KRAS-mutations in tumor tissue. KRAS-wild-type CRC patients showed a positive response rate of about 70% to cetuximab or panitumumab combined with chemotherapy. MiRNAs are promising markers in oncology and could improve our knowledge on pathogenesis and drug resistance in CRC patients. This class of molecules represents an opportunity for the development of miRNA-based strategies to overcome the ineffectiveness of anti-EGFR therapy. We performed an integrative analysis of miRNA expression profile between KRAS-mutated CRC and KRAS-wildtype CRC and paired normal colic tissue (NCT). We revealed an overexpression of miR-425-5p in KRAS-mutated CRC compared to KRAS-wild type CRC and NCT and demonstrated that miR-425-5p exerts regulatory effects on target genes involved in cellular proliferation, migration, invasion, apoptosis molecular networks. These epigenetic mechanisms could be responsible of the strong aggressiveness of KRAS-mutated CRC compared to KRAS-wildtype CRC. We proved that some miR-425-5p targeted genes are involved in EGFR tyrosine kinase inhibitor resistance pathway, suggesting that therapies based on miR-425-5p may have strong potential in targeting KRAS-driven CRC. Moreover, we demonstrated a role in the oncogenesis of miR-31-5p, miR-625-5p and miR-579 by comparing CRC versus NCT. Our results underlined that miR-425-5p might act as an oncogene to participate in the pathogenesis of KRAS-mutated CRC and contribute to increase the aggressiveness of this subcategory of CRC, controlling a complex molecular network.

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Integrated Analysis of miRNA and mRNA Endorses a Twenty miRNAs Signature for Colorectal Carcinoma

International Journal of Molecular Sciences, 2019

Colorectal cancer (CRC) ranks as the most frequent carcinoma worldwide. CRC patients show strong ... more Colorectal cancer (CRC) ranks as the most frequent carcinoma worldwide. CRC patients show strong prognostic differences and responses to treatment, and 20% have incurable metastatic disease at diagnosis. We considered it essential to investigate mechanisms that control cellular regulatory networks, such as the miRNA–mRNA interaction, known to be involved in cancer pathogenesis. We conducted a human miRNome analysis by TaqMan low density array, comparing CRC to normal colon tissue (NCT, and experimentally identified gene targets of miRNAs deregulated, by anti-correlation analysis, with the CRC whole-transcriptome profile obtained from RNASeq experiments. We identified an integrated signature of 20 deregulated miRNAs in CRC. Enrichment analyses of the gene targets controlled by these miRNAs brought to light 25 genes, members of pathways known to lead to cell growth and death (CCND1, NKD1, FZD3, MAD2L1, etc.), such as cell metabolism (ACSL6, PRPS1-2). A screening of prognosis-mediated ...

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Population structure of modern-day Italians reveals patterns of ancient and archaic ancestries in Southern Europe

European populations display low genetic diversity as the result of long term blending of the sma... more European populations display low genetic diversity as the result of long term blending of the small number of ancient founding ancestries. However it is still unclear how the combination of ancient ancestries related to early European foragers, Neolithic farmers and Bronze Age nomadic pastoralists can fully explain genetic variation across Europe. Populations in natural crossroads like the Italian peninsula are expected to recapitulate the overall continental diversity, but to date have been systematically understudied. Here we characterised the ancestry profiles of modern-day Italian populations using a genome-wide dataset representative of modern and ancient samples from across Italy, Europe and the rest of the world. Italian genomes captured several ancient signatures, including a non-steppe related substantial ancestry contribution ultimately from the Caucasus. Differences in ancestry composition as the result of migration and admixture generated in Italy the largest degree of p...

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