Abstract
The Alzheimer’s disease “inflammation hypothesis” has emerged only recently, suggesting the risk of developing AD might be influenced by variants of genes encoding for inflammatory mediators. In order to investigate in this direction, genomic DNA from 194 Italian AD cases and 454 healthy controls matched by gender and ethnicity was analyzed for the Receptor for Advanced Glycation End products (RAGE, HLA class III-centromere portion) -374 and - 429 SNPs and for the Tumor Necrosis Factor-alpha (TNF-α, HLA class III-telomere portion) -857, -308 and -238 SNPs by RFLP and Real Time PCR. Our data show statistically significant deviations between AD patients and healthy controls concerning RAGE -374 SNP genotype (TT: p=0.0084) and allele (T, A: p=0.0081) frequencies; TNF-α -308 SNP AA genotype (p=0.0433) and TNF-α -238 SNP genotype (GG: p=0.0138) and allele (G, A: p=0.0151) frequencies. Furthermore, significant differences between the study groups and regarding RAGE TC (p=0.05) and AC (p=0.009) haplotypes are present, while TNF-α haplotype reconstruction point out a statistically significant difference between patients and controls regarding AGG haplotype (p=0.002). Finally, from the combination of the individually significant SNPs of the two genes (RAGE -374, TNF-α -238 and -308) we performed an HLA class III haplotype reconstruction finding significant differences between AD subjects and controls regarding the TAG (p=0.019) and TGA (p=0.008) haplotypes. The implication of these haplotypes with the disease points to a possible involvement of entire HLA class III region in AD susceptibility.
Keywords: Alzheimer’s disease, inflammation, HLA class III.
Current Alzheimer Research
Title:The Human Leukocyte Antigen Class III Haplotype Approach: New Insight in Alzheimer's Disease Inflammation Hypothesis
Volume: 10 Issue: 10
Author(s): Elisa Maggioli, Chiara Boiocchi, Michele Zorzetto, Elena Sinforiani, Cristina Cereda, Giovanni Ricevuti and Mariaclara Cuccia
Affiliation:
Keywords: Alzheimer’s disease, inflammation, HLA class III.
Abstract: The Alzheimer’s disease “inflammation hypothesis” has emerged only recently, suggesting the risk of developing AD might be influenced by variants of genes encoding for inflammatory mediators. In order to investigate in this direction, genomic DNA from 194 Italian AD cases and 454 healthy controls matched by gender and ethnicity was analyzed for the Receptor for Advanced Glycation End products (RAGE, HLA class III-centromere portion) -374 and - 429 SNPs and for the Tumor Necrosis Factor-alpha (TNF-α, HLA class III-telomere portion) -857, -308 and -238 SNPs by RFLP and Real Time PCR. Our data show statistically significant deviations between AD patients and healthy controls concerning RAGE -374 SNP genotype (TT: p=0.0084) and allele (T, A: p=0.0081) frequencies; TNF-α -308 SNP AA genotype (p=0.0433) and TNF-α -238 SNP genotype (GG: p=0.0138) and allele (G, A: p=0.0151) frequencies. Furthermore, significant differences between the study groups and regarding RAGE TC (p=0.05) and AC (p=0.009) haplotypes are present, while TNF-α haplotype reconstruction point out a statistically significant difference between patients and controls regarding AGG haplotype (p=0.002). Finally, from the combination of the individually significant SNPs of the two genes (RAGE -374, TNF-α -238 and -308) we performed an HLA class III haplotype reconstruction finding significant differences between AD subjects and controls regarding the TAG (p=0.019) and TGA (p=0.008) haplotypes. The implication of these haplotypes with the disease points to a possible involvement of entire HLA class III region in AD susceptibility.
Export Options
About this article
Cite this article as:
Maggioli Elisa, Boiocchi Chiara, Zorzetto Michele, Sinforiani Elena, Cereda Cristina, Ricevuti Giovanni and Cuccia Mariaclara, The Human Leukocyte Antigen Class III Haplotype Approach: New Insight in Alzheimer's Disease Inflammation Hypothesis, Current Alzheimer Research 2013; 10 (10) . https://dx.doi.org/10.2174/15672050113106660169
DOI https://dx.doi.org/10.2174/15672050113106660169 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Endothelial Dysfunction and Coronary Atherosclerosis
Current Drug Targets - Cardiovascular & Hematological Disorders PCSK9 Inhibitors for the Management of Dyslipidemia in People with Type 2 Diabetes: How Low is Too Low?
Current Pharmaceutical Design Oxidative Stress and Antioxidant Potential of One Hundred Medicinal Plants
Current Topics in Medicinal Chemistry Inhibition of Tau Protein Aggregation by Rhodanine-based Compounds Solubilized Via Specific Formulation Additives to Improve Bioavailability and Cell Viability
Current Alzheimer Research Relevance of Aβ 1-42 Intrahippocampal Injection as An Animal Model of Inflamed Alzheimers Disease Brain
Current Alzheimer Research Nuclear Medicine: Proof of Principle for Targeted Drugs in Diagnosis and Therapy
Current Pharmaceutical Design Pharmacological Cyclin-Dependent Kinase Inhibitors (PCIs) as Potential Antiviral Drugs
Anti-Infective Agents in Medicinal Chemistry A Systems Biology Consideration of the Vasculopathy of Sickle Cell Anemia: The Need for Multi-Modality Chemo-Prophylaxis
Cardiovascular & Hematological Disorders-Drug Targets An Update on New Cholesterol Inhibitor: Bempedoic Acid
Current Cardiology Reviews Children with Chronic Kidney Disease and Hypertension: Could Hypertension Footprints be Early Biomarkers?
Current Hypertension Reviews Familial Mutations and Post-translational Modifications of UCH-L1 in Parkinson's Disease and Neurodegenerative Disorders
Current Protein & Peptide Science Adrenomedullin as a Potential Therapeutic Agent for Inflammatory Bowel Disease
Current Protein & Peptide Science Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease
Current Alzheimer Research Cholesterol in Alzheimers Disease: Unresolved Questions
Current Alzheimer Research rs3851179G>A in PICALM is Protective Against Alzheimer’s Disease in Five Different Countries Surrounding the Mediterranean
Current Aging Science Plombage: A Forgotten Surgical Treatment for Pulmonary Tuberculosis
Current Respiratory Medicine Reviews Dehydroevodiamine•HCl Protects Against Memory Impairment and Cerebral Amyloid-β Production in Tg2576 Mice by Acting as a β-Secretase Inhibitor
CNS & Neurological Disorders - Drug Targets New Insights into the Roles of Endolysosomal Cathepsins in the Pathogenesis of Alzheimers Disease: Cathepsin Inhibitors as Potential Therapeutics
CNS & Neurological Disorders - Drug Targets Genetic Polymorphism of LDLR (rs688) is Associated with Primary Intracerebral Hemorrhage
Current Neurovascular Research Meet Our Editorial Board Member:
Current Alzheimer Research