Synergistic influence of cytokine gene polymorphisms over the risk of dementia: A multifactor dimensionality reduction analysis

ObjectiveEvidence supports the important role of neuroinflammation in some types of dementia. This study aimed to evaluate the effect of epistasis of gene cytokines such as interleukin (IL)-alpha, IL-6, tumor necrosis factor (TNF alpha), and interferon-gamma (IFN-gamma) on the susceptibility to the development of dementia. Materials and methodsIn the study, 221 patients diagnosed with dementia and 710 controls were included. The multifactor-dimensionality reduction (MDR) analysis was performed to identify the epistasis between SNP located in genes of IL-alpha (rs1800587), IL-6 (rs1800796), TNF alpha (rs361525 and rs1800629), and IFN gamma (rs2069705). The best risk prediction model was identified based on precision and cross-validation consistency. ResultsMultifactor-dimensionality reduction analysis detected a significant model with the genes TNF alpha, IFN gamma, IL1 alpha, and IL6 (prediction success: 72%, p < 0.0001). When risk factors were analyzed with these polymorphisms, the model achieved a similar prediction for dementia as the genes-only model. ConclusionThese data indicate that gene-gene interactions form significant models to identify populations susceptible to dementia

Association between APOE-ε(4) Carrier Status and Qualitative Neuroimaging Characteristics in Older Adults with Mild Cognitive Impairment

BACKGROUND: The pathogenesis of mild cognitive impairment (MCI) is multifactorial and includes the presence of genetic variants such as the ε(4) allele of the apolipoprotein E gene (APOE-ε(4)). Association between the APOE-ε(4) carrier status and deleterious structural and functional changes on magnetic resonance imaging (MRI) has been previously described in individuals with Alzheimer's disease. However, the central nervous system changes may possibly develop in earlier stages of cognitive impairment, as reflected in MCI. OBJECTIVE: The objective of the study was to determine the association between APOE-ε(4) carrier status and qualitative changes on MRI (medial temporal and parietal atrophy), as well as the detection of white matter hyperintensities (WMH) in older adults with MCI, in the memory clinic of a tertiary care hospital in Mexico City. METHODS: A cross-sectional study of 72 adults aged 60 years or above who underwent an exhaustive clinical, neuroimaging, and neuropsychological evaluation. Multivariate logistic regression models were constructed to determine the association between APOE-ε(4) carrier status and qualitative/quantitative changes on MRI. RESULTS: Mean age was 75.2 years (± 7.2) and 64% were female. Twenty-one participants were cognitively normal and 51 had MCI. Almost 56% were APOE-ε(4) carriers and were associated with medial-temporal atrophy according to the Scheltens scale (odds ratio [OR]: 20.0, 95% confidence intervals [CI]: 3.03-131.7), parietal atrophy according to the Koedam's score (OR: 6.3; 95% CI 1.03-39.53), and WMH according to the Fazekas scale (OR: 11.7, 95% CI: 1.26-108.2), even after adjusting for age, educational level, and cardiovascular risk factors. CONCLUSION: The APOE-ε(4) carrier status was associated with medial temporal and parietal atrophy, as well as WMH. Our findings support the hypothesis suggesting the contribution of this genotype to neurodegeneration and cerebral vascular pathology

Angiotensin-Converting Enzyme Gene (ACE) Insertion/Deletion Polymorphism in Mexican Populations

The angiotensin-converting enzyme gene (ACE) insertion/dele- tion polymorphism was determined in 211 Mexican healthy individuals be- longing to different Mexican ethnic groups (98 Mestizos, 64 Teenek, and 49 Nahuas). ACE polymorphism differed among Mexicans with a high frequen- cy of the D allele and the D/D genotype in Mexican Mestizos. The D/D geno- type was absent in Teenek and present in only one Nahua individual (2.0%). When comparisons were made, we observed that Caucasian, African, and Asian populations presented the highest frequencies of the D allele, whereas Amerindian (Teenek and Pima) and Australian Aboriginals showed the high- est frequencies of the I allele. The distribution of I/D genotype was heteroge- neous in all populations: Australian Aboriginals presented the lowest fre- quency (4.9%), whereas Nahuas presented the highest (73.4%). The present study shows the frequencies of a polymorphism not analyzed previously in Mexican populations and establishes that this polymorphism distinguishes the Amerindian populations of other groups. On the other hand, since ACE alleles have been associated with genetic susceptibility to developing cardio- vascular diseases and hypertension, knowledge of the distribution of these al- leles could help to define the true significance of ACE polymorphism as a ge- netic susceptibility marker in the Amerindian populations