ORCID Profile
0000-0002-9284-5953
Current Organisations
Università degli Studi della Campania Luigi Vanvitelli Dipartimento di Medicina Sperimentale
,
University of Milan
,
Università degli Studi di Milano
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Publications
A novel Alzheimer disease locus located near the gene encoding tau protein
Publisher: Springer Science and Business Media LLC
Date: 17-03-2015
DOI: 10.1038/MP.2015.23
Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer's and Parkinson's diseases
Publisher: BMJ
Date: 29-11-2016
TREM2 regulates microglial cell activation in response to demyelination in vivo
Publisher: Springer Science and Business Media LLC
Date: 29-01-2015
Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk
Publisher: Elsevier BV
Date: 11-2018
Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis
Publisher: Wiley
Date: 07-06-2013
Inflammatory expression profile in peripheral blood mononuclear cells from patients with Nasu-Hakola Disease
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.CYTO.2018.12.024
Abstract: Homozygous mutations in Triggering Receptor Expressed on Myeloid cells 2 gene (TREM2) are one of the major causes of Nasu Hakola Disease (NHD). We analysed Peripheral Blood Mononuclear Cells (PBMC) profile of 164 inflammatory factors in patients with NHD carrying the TREM2 Q33X mutation as compared with heterozygous and wild type in iduals. Several molecules related to bone formation and angiogenesis were altered in NHD compared to non-carriers: Bone Morphogenetic Protein (BMP)-1 mRNA levels were significantly increased in PBMC (2.32 fold-increase P = 0.01), as were Transforming Growth Factor Beta (TGFB)3 levels (1.51 fold-increase P = 0.02). Conversely, CXCL5 and Pro Platelet Basic Protein (PPBP) were strongly downregulated (-28.26, -9.85 fold-decrease over non-carriers, respectively, P = 0.01), as well as Platelet Factor 4 Variant 1 (PF4V1 -41.44, P = 0.03). Among other inflammatory factors evaluated, Interleukin (IL)-15 and Tumor Necrosis Factor Superfamily Member (TNFSF)4 mRNA levels were decreased in NHD as compared with non-carriers (-2.25 and -3.87 fold-decrease, P = 0.01 and 0.001, respectively). In heterozygous in iduals, no significant differences were observed, apart from IL-15 mRNA levels, that were decreased at the same extent as NHD (-2.05 fold-decrease over non-carriers, P = 0.002). We identified a signature in PBMC from patients with NHD consisting of strongly decreased mRNA levels of CXCL5, PPBP, PF4V1, mildly decreased IL-15 and TNFSF4 and mildly increased BMP-1 and TGFB3.
Cerebrospinal fluid progranulin levels in patients with different multiple sclerosis subtypes
Publisher: Elsevier BV
Date: 2010
CLIC1 Protein Accumulates in Circulating Monocyte Membrane during Neurodegeneration
Publisher: MDPI AG
Date: 21-02-2020
DOI: 10.3390/IJMS21041484
Abstract: Pathologies that lead to neurodegeneration in the central nervous system (CNS) represent a major contemporary medical challenge. Neurodegenerative processes, like those that occur in Alzheimer’s disease (AD) are progressive, and at the moment, they are unstoppable. Not only is an adequate therapy missing but diagnosis is also extremely complicated. The most reliable method is the measurement of beta amyloid and tau peptides concentration in the cerebrospinal fluid (CSF). However, collecting liquid s les from the CNS is an invasive procedure, thus it is not suitable for a large-scale prevention program. Ideally, blood testing is the most manageable and appropriate diagnostic procedure for a massive population screening. Recently, a few candidates, including proteins or microRNAs present in plasma/serum have been identified. The aim of the present work is to propose the chloride intracellular channel 1 (CLIC1) protein as a potential marker of neurodegenerative processes. CLIC1 protein accumulates in peripheral blood mononuclear cells (PBMCs), and increases drastically when the CNS is in a chronic inflammatory state. In AD patients, both immunolocalization and mRNA quantification are able to show the behavior of CLIC1 during a persistent inflammatory state of the CNS. In particular, confocal microscopy analysis and electrophysiological measurements highlight the significant presence of transmembrane CLIC1 (tmCLIC1) in PBMCs from AD patients. Recent investigations suggest that tmCLIC1 has a very specific role. This provides an opportunity to use blood tests and conventional technologies to discriminate between healthy in iduals and patients with ongoing neurodegenerative processes.
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
Publisher: Springer Science and Business Media LLC
Date: 07-06-2021
DOI: 10.1038/S41467-021-22491-8
Abstract: Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select in iduals at high risk of Alzheimer’s disease.
CSF biomarker variability in the Alzheimer's Association quality control program
Publisher: Wiley
Date: 05-2013
Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease
Publisher: Wiley
Date: 16-03-2016
SELPLG and SELP single-nucleotide polymorphisms in multiple sclerosis
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.NEULET.2005.10.014
Abstract: P-Selectin (SELP) and P-selectin glycoprotein ligand-1 (SELPLG) constitute a receptor/ligand complex involved in the recruitment of activated lymphocytes, a critical event in the pathogenesis of multiple sclerosis (MS). In order to determine whether genetic variation in these pivotal molecules influences susceptibility to MS, we genotyped 214 Italian patients compared with 220 Italian controls for three single-nucleotide polymorphisms (SNPs): SELPLG Met62Ile, SELP C-2123G and SELP Thr715Pro. No significant differences in both SELP SNPs were found between patients and controls, whereas a decreased frequency of the Met62Ile SNP was found in patients versus controls in the Italian population (P = 0.025). To confirm these preliminary findings, the Met62Ile SNP was analysed in 938 UK trio families. This SNP did not show evidence for association with susceptibility to MS in the larger UK cohort. Therefore, none of the SNPs investigated is associated with MS, although this analysis does not conclusively exclude SELPLG and SELP as genetic risk factors for MS as much variation remains untested.
Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
Publisher: Public Library of Science (PLoS)
Date: 12-06-2014
The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers
Publisher: Wiley
Date: 07-2011
Differential early subcortical involvement in genetic FTD within the GENFI cohort
Publisher: Elsevier BV
Date: 2021
Author Correction: Susceptible genes and disease mechanisms identified in frontotemporal dementia and frontotemporal dementia with Amyotrophic Lateral Sclerosis by DNA-methylation and GWAS
Publisher: Springer Science and Business Media LLC
Date: 14-05-2018
DOI: 10.1038/S41598-018-21308-X
Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
A second update on mapping the human genetic architecture of COVID-19
Publisher: Springer Science and Business Media LLC
Date: 06-09-2023
New insights into the genetic etiology of Alzheimer’s disease and related dementias
Publisher: Springer Science and Business Media LLC
Date: 04-2022
DOI: 10.1038/S41588-022-01024-Z
Abstract: Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
Convergent genetic and expression data implicate immunity in Alzheimer's disease
Publisher: Wiley
Date: 19-12-2014
CXCR4 involvement in neurodegenerative diseases
Publisher: Springer Science and Business Media LLC
Date: 11-04-2018
DOI: 10.1038/S41398-017-0049-7
Abstract: Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared genetic risk across several neurodegenerative diseases. Using genome-wide association data from large studies (total n = 82,337 cases and controls), we utilized a previously validated approach to identify genetic overlap and reveal common pathways between progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson’s disease (PD) and Alzheimer’s disease (AD). In addition to the MAPT H1 haplotype, we identified a variant near the chemokine receptor CXCR4 that was jointly associated with increased risk for PSP and PD. Using bioinformatics tools, we found strong physical interactions between CXCR4 and four microglia related genes, namely CXCL12 , TLR2, RALB, and CCR5 . Evaluating gene expression from post-mortem brain tissue, we found that expression of CXCR4 and microglial genes functionally related to CXCR4 was dysregulated across a number of neurodegenerative diseases. Furthermore, in a mouse model of tauopathy, expression of CXCR4 and functionally associated genes was significantly altered in regions of the mouse brain that accumulate neurofibrillary tangles most robustly. Beyond MAPT , we show dysregulation of CXCR4 expression in PSP, PD, and FTD brains, and mouse models of tau pathology. Our multi-modal findings suggest that abnormal signaling across a ‘network’ of microglial genes may contribute to neurodegeneration and may have potential implications for clinical trials targeting immune dysfunction in patients with neurodegenerative diseases.
T cells producing GM-CSF and IL-13 are enriched in the cerebrospinal fluid of relapsing MS patients
Publisher: SAGE Publications
Date: 25-06-2019
Abstract: Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune demyelinating disease. Its pathogenesis involves humoral and cellular immunity, with production of pro- and anti-inflammatory cytokines by T cells. To analyze the cytokine profile of cerebrospinal fluid (CSF) T cells in patients with relapsing-remitting MS (RRMS) and non-inflammatory controls. T cell cytokine production was analyzed by flow cytometry in CSF s les collected from 34 untreated RRMS patients and 20 age-matched controls. Immunofluorescence studies were performed in spinal cord MS active lesions. Percentages of CSF-derived IL-17A, IL-17A/IL-22, and IL-17A/GM-CSF producing T cells were significantly higher in RRMS patients compared to controls. Percentages of T cells producing IFN-γ were lower in RRMS patients compared to controls. Patients in relapse showed higher percentages of CD4 + T cells producing IL-13 and GM-CSF compared to patients in remission. We found a positive correlation between percentages of IL-13 + T cells and the Expanded Disability Status Scale (EDSS ρ = 0.5 p 0.05). Meningeal IL-13-producing T cells were detected in spinal cord MS active lesions. We observed differences in IL-17, IL-22, and IFN-γ production by CSF T cells in RRMS versus controls and a positive correlation between IL-13-producing T cells and EDSS in RRMS patients.
Detailed stratified GWAS analysis for severe COVID-19 in four European populations
Publisher: Oxford University Press (OUP)
Date: 15-07-2022
DOI: 10.1093/HMG/DDAC158
Abstract: Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian in iduals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
Postoperative patient-controlled analgesia: Meta-analyses of initial randomized control trials
Publisher: Elsevier BV
Date: 05-1993
DOI: 10.1016/0952-8180(93)90013-5
Abstract: To compare outcomes during conventional analgesia (as-needed intramuscular dosing) and patient-controlled analgesia (PCA) in postoperative patients by analyzing data from published comparative trials. Meta-analyses of 15 randomized control trials. Seven hundred eighty-seven adult patients (aged 16 to 65) undergoing various operative procedures. Either PCA or conventional analgesia for postoperative pain control. Data were extracted on analgesic efficacy, analgesic use, patient satisfaction, length of hospital stay, and side effects. Meta-analyses of the data showed the following: (1) greater analgesic efficacy when PCA was used, with a mean additional benefit of 5.6 on a scale of 0 to 100 (SED, 2.2 p = 0.006) (2) a nonsignificant trend toward reduced analgesic use in PCA patients, based on a count of trials finding in one direction or the other (p = 0.092) (3) a 42% difference in the proportion of patients expressing satisfaction over dissatisfaction (SED, 20% p = 0.02), with PCA being preferred (4) a nonsignificant trend toward shortening of length of hospital stay with PCA use (mean, 0.15 days, SED, 0.13 p = 0.24) (5) no significant differences in the occurrence of any side effect. Patient preference strongly favors PCA over conventional analgesia. Patients using PCA also obtain better pain relief than those using conventional analgesia, without an increase in side effects. Favorable effect of PCA upon analgesic usage and length of hospital stay did not in the initial trials attain statistical significance. Nonetheless, the favorable trends in the mean effect sizes for both outcomes argue that further studies of both outcomes should be performed to determine whether the favorable impact of PCA upon either may become statistically significant if larger numbers of patients are enrolled.
Hierarchical spectral clustering reveals brain size and shape changes in asymptomatic carriers of C9orf72
Publisher: Oxford University Press (OUP)
Date: 04-07-2022
DOI: 10.1093/BRAINCOMMS/FCAC182
Abstract: Traditional methods for detecting asymptomatic brain changes in neurodegenerative diseases such as Alzheimer’s disease or frontotemporal degeneration typically evaluate changes in volume at a predefined level of granularity, e.g. voxel-wise or in a priori defined cortical volumes of interest. Here, we apply a method based on hierarchical spectral clustering, a graph-based partitioning technique. Our method uses multiple levels of segmentation for detecting changes in a data-driven, unbiased, comprehensive manner within a standard statistical framework. Furthermore, spectral clustering allows for detection of changes in shape along with changes in size. We performed tensor-based morphometry to detect changes in the Genetic Frontotemporal dementia Initiative asymptomatic and symptomatic frontotemporal degeneration mutation carriers using hierarchical spectral clustering and compared the outcome to that obtained with a more conventional voxel-wise tensor- and voxel-based morphometric analysis. In the symptomatic groups, the hierarchical spectral clustering-based method yielded results that were largely in line with those obtained with the voxel-wise approach. In asymptomatic C9orf72 expansion carriers, spectral clustering detected changes in size in medial temporal cortex that voxel-wise methods could only detect in the symptomatic phase. Furthermore, in the asymptomatic and the symptomatic phases, the spectral clustering approach detected changes in shape in the premotor cortex in C9orf72. In summary, the present study shows the merit of hierarchical spectral clustering for data-driven segmentation and detection of structural changes in the symptomatic and asymptomatic stages of monogenic frontotemporal degeneration.
Mapping the human genetic architecture of COVID-19
Publisher: Springer Science and Business Media LLC
Date: 08-07-2021
DOI: 10.1038/S41586-021-03767-X
Abstract: The genetic make-up of an in idual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease
Publisher: Springer Science and Business Media LLC
Date: 03-07-2202
DOI: 10.1038/NG.803
APOE and Alzheimer disease: a major gene with semi-dominant inheritance
Publisher: Springer Science and Business Media LLC
Date: 10-05-2011
DOI: 10.1038/MP.2011.52
Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies
Publisher: Public Library of Science (PLoS)
Date: 09-01-2018
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
Publisher: Springer Science and Business Media LLC
Date: 17-07-2017
DOI: 10.1038/NG.3916
Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference.
Publisher: Springer Science and Business Media LLC
Date: 15-10-2018
DOI: 10.1038/S41467-018-05892-0
Abstract: The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique—Subtype and Stage Inference (SuStaIn)—able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes further the technique reveals within-genotype heterogeneity. In Alzheimer’s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype ( p = 7.18 × 10 −4 ) or temporal stage ( p = 3.96 × 10 −5 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine.
Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation
Publisher: Oxford University Press (OUP)
Date: 12-09-2008
DOI: 10.1093/BRAIN/AWN217
Progression of Behavioral Disturbances and Neuropsychiatric Symptoms in Patients With Genetic Frontotemporal Dementia
Publisher: American Medical Association (AMA)
Date: 06-01-2021
Candidate gene analysis of selectin cluster in patients with multiple sclerosis
Publisher: Springer Science and Business Media LLC
Date: 25-02-2009
DOI: 10.1007/S00415-009-5016-7
Abstract: Three single nucleotide polymorphisms (SNPs) with a potential impact on the function of selectins (rs6133, rs4987310 and rs5368 substitutions localized in the coding regions of P-sel, L-sel and E-sel, respectively) were analyzed in an Italian population of 165 patients with multiple sclerosis (MS) as compared with 149 controls and in a replication American population of Caucasian descent consisting of 122 patients and 50 controls. No significant differences in either allelic or genotypic frequency in all the SNPs tested were found in the Italian population. A tendency to an increased frequency of the rs6133 T allele was observed in the American population, but applying the Bonferroni correction the significance threshold was not reached. Haploview analysis demonstrated that rs4987310 and rs5368 markers are in strong LD (D' = 0.97) in both populations. Combining the two SNPs, we found no difference in haplotype distribution in patients compared with controls, either in Italian or in American population. Despite the fact that selectins play a role in the pathogenesis of MS and their encoding genes are located in regions associated with the disease, the selectin gene cluster studied likely does not influence the susceptibility to MS in Caucasians.
Decreased circulating miRNA levels in patients with primary progressive multiple sclerosis
Publisher: SAGE Publications
Date: 25-11-2013
Abstract: Emerging evidence underlines the importance of micro(mi)RNAs in the pathogenesis of multiple sclerosis (MS). Free-circulating miRNAs were investigated in serum from MS patients compared to controls. Statistically significant decreased levels of miR-15b, miR-23a and miR-223 were observed in MS patients ( p 0.05). Results were validated and replicated in two further independent MS populations. A direct correlation between miRNA levels and the EDSS score was determined in PPMS ( p 0.007). The generalized trend toward miRNA down-regulation could result in over-expression of target genes involved in disease pathogenesis. Circulating miRNA profiling could thus represent a new avenue to identify easily detectable disease biomarkers.
Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
Publisher: Springer Science and Business Media LLC
Date: 09-02-2023
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
Publisher: Springer Science and Business Media LLC
Date: 29-09-2013
DOI: 10.1038/NG.2770
E-selectin A561C and G98T polymorphisms influence susceptibility and course of multiple sclerosis
Publisher: Elsevier BV
Date: 08-2005
DOI: 10.1016/J.JNEUROIM.2005.05.003
Abstract: Three hundred seven patients with MS and 300 controls were genotyped for G98T and A561C SNPs in the E-selectin gene, and genetic data were correlated with the course of the disease. The frequency of the T/T genotype of the G98T SNP was significantly increased in RR-MS patients compared with controls, while was absent in PP-MS. The frequency of the A561C SNP was significantly decreased in SP-MS compared with benign RR-MS. The T/T genotype of the G98T SNP is likely to confer an increased risk to develop MS. The A561C polymorphism seems to act as protective factor towards the progression to SP-MS.
Progranulin gene variability increases the risk for primary progressive multiple sclerosis in males
Publisher: Springer Science and Business Media LLC
Date: 13-05-2010
DOI: 10.1038/GENE.2010.18
Abstract: Progranulin (GRN) gene variability has been analyzed in a s le of 354 patients with multiple sclerosis (MS) compared with 343 controls. No significant differences were observed, but by stratifying according to MS subtypes, a significant increased frequency of the rs2879096 TT genotype was found in primary progressive MS (PPMS) patients versus controls (16.0 vs 3.5%, P=0.023, odds ratio (OR) 5.2, 95% confidence interval (CI) 1.2-21.4). In addition, in PPMS, an association with the C allele of rs4792938 was observed (55.3 vs 33.5%, P=0.011, OR 2.4, 95% CI 1.2-4.7). An independent population was studied as replication, failing to confirm results previously obtained. Stratifying according to gender, an association with rs4792938 C allele was found in male PPMS patients compared with controls (40.7 vs 26.9%, P=0.002, OR 1.87, 95% CI 1.2-2.8). An association with the rs2879096T allele was observed (29.2 in patients compared with 18.9% in controls, P=0.012, OR 1.77, 95% CI 1.1-2.8). Haplotype analysis showed that TC haplotype frequency is increased in PPMS male patients compared with male controls (25.7 vs 16.6% P=0.02, OR 1.69, 95% CI 1.1-2.7), whereas the respective GC haplotype seems to exert a protective effect, as its frequency is decreased in patients compared with controls (55.8% vs 70.9% P=0.001, OR 0.52, 95% CI 0.4-0.8). Therefore, GRN haplotypes likely influence the risk of developing PPMS in males.
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
Publisher: Springer Science and Business Media LLC
Date: 08-2011
DOI: 10.1038/NATURE10251
Related Organisations
Università Degli Studi Della Campania Luigi Vanvitelli Dipartimento Di Medicina Sperimentale
Location: Italy
Related Funding Activities
No related grants have been discovered for Daniela Galimberti.