Article

Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease: patterns of linkage disequilibrium and disease/marker association.

Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.
Genomics (Impact Factor: 2.79). 07/2007; 89(6):655-65. DOI: 10.1016/j.ygeno.2007.02.002
Source: PubMed

ABSTRACT The epsilon(4) allele of APOE confers a two- to fourfold increased risk for late-onset Alzheimer's disease (LOAD), but LOAD pathology does not all fit neatly around APOE. It is conceivable that genetic variation proximate to APOE contributes to LOAD risk. Therefore, we investigated the degree of linkage disequilibrium (LD) for a comprehensive set of 50 SNPs in and surrounding APOE using a substantial Caucasian sample of 1100 chromosomes. SNPs in APOE were further molecularly haplotyped to determine their phases. One set of SNPs in TOMM40, roughly 15 kb upstream of APOE, showed intriguing LD with the epsilon(4) allele and was strongly associated with the risk for developing LOAD. However, when all the SNPs were entered into a logit model, only the effect of APOE epsilon(4) remained significant. These observations diminish the possibility that loci in the TOMM40 gene may have a major effect on the risk for LOAD in Caucasians.

0 Bookmarks
 · 
83 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human longevity results from a number of factors, including genetic background, favorable environmental, social factors and chance. In this study, we aimed to elucidate the association of human longevity with genetic variations in several major candidate genes in a Han Chinese population.
    PLoS ONE 06/2014; 9(6):e99580. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Maksimović N, I. Novaković, V. Ralić, and E.Stefanova (2013): Distribution of apolipoprotein e gene polymorphism in students and in high-educated elderly from Serbia. Genetika, Vol 45, No. 3, 865-872. Apolipoprotein E (ApoE) play important role in lipid metabolism and in processes of remodeling and reparation in central nervous system. Three common ApoE isoforms, ApoE2, ApoE3 and ApoE4, show strong genetic determination by ε2, ε3, and ε4 allele. In human genome gene encoding Apolipoprotein E (APOE) is located on cromosome 19, and ε2/ε3/ε4 haplotype system is defined by 2 non-synonymous single nucleotide polymorphisms (SNPs) in the APOE exon 4. The frequency of the three APOE alleles and corresponding genotypes varies across human populations, with possible clinical implications. At least, variable distribution of ε4 allele may contribute to the regional risk of cardiovascular and Alzheimer's diseases. Allele-frequency comparisons between younger and older populations suggest an effect of APOE on mortality, but these data are not consistently confirmed. In the present study we have analyzed the distribution of APOE gene polymorphism in a group of University students and retained University professors living in Serbia. After DNA extraction from peripheral blood samples, the APOE genotype was determined by polymerase chain reaction (PCR) followed with HhaI restriction digestion. We found no statistically significant difference in alleles and genotypes distribution between younger and elder group of participants. Also, there was no significant difference compared to APOE data previously obtained in YUSAD cohort of healthy school children (15 y of age) from different regions of Serbia. In both of our groups, as well as in YUSAD cohort, frequency of APOE ε4 allele was <10%. The observed frequencies are lower than in neighboring countries, but similar with Spanish data and some Asian populations. Our results do not support important role of APOE ε4 in the morbidity and mortality in Serbian population, but gene-environmental-social interactions should be considered.
    01/2013;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Age-related macular degeneration (AMD) is a late-onset, neurodegenerative disease. Genes related to lipid metabolism are important in AMD pathogenesis. Recently, a variant rs2075650 located in lipid metabolism-related locus APOE/TOMM40 was identified to be associated with advanced AMD and early AMD, respectively, in two genome-wide association studies with European ancestry, while no association study between rs2075650 and overall advanced AMD in Chinese population has been conducted before. We evaluated the potential effect of this variant on advanced AMD in a Han Chinese cohort with 204 advanced AMD patients and 1536 healthy controls. The results suggested that rs2075650 was neither associated with advanced AMD in allele level (P = 0.348) nor in genotype level (P = 0.890 under additive model with age and sex adjusted). In conclusion, our study did not confirm the impact of rs2075650 on advanced AMD risk, indicating that rs2075650 is unlikely a superior marker for APOE/TOMM40 susceptible region with advanced AMD in Han Chinese population.
    Experimental Biology and Medicine 10/2014; 240(2). · 2.23 Impact Factor

Preview

Download
0 Downloads
Available from