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D10S1423 identifies a susceptibility locus for Alzheimer's disease (AD7) in a prospective, longitudinal, double-blind study of asymptomatic individuals: results at 14 years.
Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 05; 153B(2):359-364.AJ

Abstract

Typical forms of Alzheimer's disease (AD) appear to be influenced by multiple susceptibility loci. This report describes the prospective, longitudinal, double-blind assessment of the age-specific risk of AD encountered by 325 asymptomatic first-degree relatives of AD probands who carried the D10S1423 (AD7) 234 bp allele, the APOE E4 allele, or both, after 14 years of systematic follow-up. A total of 30 incident cases of AD were detected during the first 3752 subject-years of surveillance. The effects of carrying either or both of the D10S1423 234 bp and APOE E4 alleles on the age-specific risk of developing AD were determined using Kaplan-Meier survival analysis. The risk of developing AD was the greatest for individuals who carried both alleles (Mantel-Cox statistic = 16.46, df = 3, P = 0.0009; Breslow statistic = 13.38, df = 3, P = 0.004). Cox proportional hazards models were developed to estimate the risk ratios for each genotype, controlling for the potential effects of age at recruitment, sex, and years of education. Only individuals who carried both risk alleles exhibited a risk ratio that differed significantly from 1 (risk ratio = 7.5, P = 0.002, 95% CI = 2.1-27.0). Neither age at recruitment, sex, nor years of education made significant contributions to the model, although women tended to be at greater risk (P = 0.06). Recent evidence that D10S1423 resides within open reading frame C10orf112, whose predicted product resembles a low-density lipoprotein receptor, suggests a molecular mechanism for this gene-gene interaction.

Authors+Show Affiliations

Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. Department of Biological Sciences, Mellon College of Science, Carnegie-Mellon University, Pittsburgh, Pennsylvania.Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19591129

Citation

Zubenko, George S., et al. "D10S1423 Identifies a Susceptibility Locus for Alzheimer's Disease (AD7) in a Prospective, Longitudinal, Double-blind Study of Asymptomatic Individuals: Results at 14 Years." American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics, vol. 153B, no. 2, 2010, pp. 359-364.
Zubenko GS, Hughes HB, Zubenko WN. D10S1423 identifies a susceptibility locus for Alzheimer's disease (AD7) in a prospective, longitudinal, double-blind study of asymptomatic individuals: results at 14 years. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(2):359-364.
Zubenko, G. S., Hughes, H. B., & Zubenko, W. N. (2010). D10S1423 identifies a susceptibility locus for Alzheimer's disease (AD7) in a prospective, longitudinal, double-blind study of asymptomatic individuals: results at 14 years. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics, 153B(2), 359-364. https://doi.org/10.1002/ajmg.b.31017
Zubenko GS, Hughes HB, Zubenko WN. D10S1423 Identifies a Susceptibility Locus for Alzheimer's Disease (AD7) in a Prospective, Longitudinal, Double-blind Study of Asymptomatic Individuals: Results at 14 Years. Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):359-364. PubMed PMID: 19591129.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - D10S1423 identifies a susceptibility locus for Alzheimer's disease (AD7) in a prospective, longitudinal, double-blind study of asymptomatic individuals: results at 14 years. AU - Zubenko,George S, AU - Hughes,Hugh B,3rd AU - Zubenko,Wendy N, PY - 2009/7/11/entrez PY - 2009/7/11/pubmed PY - 2010/12/21/medline SP - 359 EP - 364 JF - American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics JO - Am. J. Med. Genet. B Neuropsychiatr. Genet. VL - 153B IS - 2 N2 - Typical forms of Alzheimer's disease (AD) appear to be influenced by multiple susceptibility loci. This report describes the prospective, longitudinal, double-blind assessment of the age-specific risk of AD encountered by 325 asymptomatic first-degree relatives of AD probands who carried the D10S1423 (AD7) 234 bp allele, the APOE E4 allele, or both, after 14 years of systematic follow-up. A total of 30 incident cases of AD were detected during the first 3752 subject-years of surveillance. The effects of carrying either or both of the D10S1423 234 bp and APOE E4 alleles on the age-specific risk of developing AD were determined using Kaplan-Meier survival analysis. The risk of developing AD was the greatest for individuals who carried both alleles (Mantel-Cox statistic = 16.46, df = 3, P = 0.0009; Breslow statistic = 13.38, df = 3, P = 0.004). Cox proportional hazards models were developed to estimate the risk ratios for each genotype, controlling for the potential effects of age at recruitment, sex, and years of education. Only individuals who carried both risk alleles exhibited a risk ratio that differed significantly from 1 (risk ratio = 7.5, P = 0.002, 95% CI = 2.1-27.0). Neither age at recruitment, sex, nor years of education made significant contributions to the model, although women tended to be at greater risk (P = 0.06). Recent evidence that D10S1423 resides within open reading frame C10orf112, whose predicted product resembles a low-density lipoprotein receptor, suggests a molecular mechanism for this gene-gene interaction. SN - 1552-485X UR - https://www.unboundmedicine.com/medline/citation/19591129/D10S1423_identifies_a_susceptibility_locus_for_Alzheimer's_disease__AD7__in_a_prospective_longitudinal_double_blind_study_of_asymptomatic_individuals:_results_at_14_years_ L2 - https://doi.org/10.1002/ajmg.b.31017 DB - PRIME DP - Unbound Medicine ER -