Tags

Type your tag names separated by a space and hit enter

Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease.
Hum Mol Genet. 2006 Jul 01; 15(13):2170-82.HM

Abstract

The apolipoprotein E (APOE) gene has been consistently shown to be a major genetic risk factor; however, all cases of Alzheimer's disease (AD) cannot be attributed to the epsilon4 variant of APOE, because about half of AD patients have the APOE-epsilon3*3 genotype. To identify an additional genetic risk factor(s), we performed large-scale single nucleotide polymorphism (SNP)-based association analysis of 1526 late-onset AD patients and 1666 control subjects in a Japanese population. We prepared two independent sets consisting of exploratory and validation samples, respectively, with only the APOE-epsilon3*3 genotype, and first carried out genotyping for the exploratory set with 1206 SNPs in the region between 60 and 107 Mb on chromosome 10q that is implicated by linkage studies as containing an AD susceptibility locus. Thirty-five SNPs that showed significant values (P<0.01) were followed-up to detect any association with the validation samples. Finally, six SNPs exhibited replicated significant associations (P=0.000035-0.00048) on meta-analysis of both sets. These SNPs were clustered in a locus spanning 220 kb at genomic position 101 Mb, and three of the six SNPs were located in the dynamin-binding protein (DNMBP) gene. Quantitative real-time RT-PCR analysis demonstrated that neuropathologically confirmed AD brains exhibit a significant reduction of DNMBP mRNA compared with age-matched ones (P<0.0169). Thus, we confirmed the association of DNMBP with AD individuals with the APOE-epsilon3*3 genotype or lacking the epsilon4 allele, and DNMBP may be one of the susceptibility genes for AD.

Authors+Show Affiliations

Genome Science Branch, Center for Bioresource-Based Researches, Brain Research Institute, Niigata University, Niigata, Japan. ryosun@gene.med.niigata-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16740596

Citation

Kuwano, Ryozo, et al. "Dynamin-binding Protein Gene On Chromosome 10q Is Associated With Late-onset Alzheimer's Disease." Human Molecular Genetics, vol. 15, no. 13, 2006, pp. 2170-82.
Kuwano R, Miyashita A, Arai H, et al. Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease. Hum Mol Genet. 2006;15(13):2170-82.
Kuwano, R., Miyashita, A., Arai, H., Asada, T., Imagawa, M., Shoji, M., Higuchi, S., Urakami, K., Kakita, A., Takahashi, H., Tsukie, T., Toyabe, S., Akazawa, K., Kanazawa, I., & Ihara, Y. (2006). Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease. Human Molecular Genetics, 15(13), 2170-82.
Kuwano R, et al. Dynamin-binding Protein Gene On Chromosome 10q Is Associated With Late-onset Alzheimer's Disease. Hum Mol Genet. 2006 Jul 1;15(13):2170-82. PubMed PMID: 16740596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease. AU - Kuwano,Ryozo, AU - Miyashita,Akinori, AU - Arai,Hiroyuki, AU - Asada,Takashi, AU - Imagawa,Masaki, AU - Shoji,Mikio, AU - Higuchi,Susumu, AU - Urakami,Katsuya, AU - Kakita,Akiyoshi, AU - Takahashi,Hitoshi, AU - Tsukie,Tamao, AU - Toyabe,Shinichi, AU - Akazawa,Kohei, AU - Kanazawa,Ichiro, AU - Ihara,Yasuo, AU - ,, Y1 - 2006/06/01/ PY - 2006/6/3/pubmed PY - 2006/9/6/medline PY - 2006/6/3/entrez SP - 2170 EP - 82 JF - Human molecular genetics JO - Hum Mol Genet VL - 15 IS - 13 N2 - The apolipoprotein E (APOE) gene has been consistently shown to be a major genetic risk factor; however, all cases of Alzheimer's disease (AD) cannot be attributed to the epsilon4 variant of APOE, because about half of AD patients have the APOE-epsilon3*3 genotype. To identify an additional genetic risk factor(s), we performed large-scale single nucleotide polymorphism (SNP)-based association analysis of 1526 late-onset AD patients and 1666 control subjects in a Japanese population. We prepared two independent sets consisting of exploratory and validation samples, respectively, with only the APOE-epsilon3*3 genotype, and first carried out genotyping for the exploratory set with 1206 SNPs in the region between 60 and 107 Mb on chromosome 10q that is implicated by linkage studies as containing an AD susceptibility locus. Thirty-five SNPs that showed significant values (P<0.01) were followed-up to detect any association with the validation samples. Finally, six SNPs exhibited replicated significant associations (P=0.000035-0.00048) on meta-analysis of both sets. These SNPs were clustered in a locus spanning 220 kb at genomic position 101 Mb, and three of the six SNPs were located in the dynamin-binding protein (DNMBP) gene. Quantitative real-time RT-PCR analysis demonstrated that neuropathologically confirmed AD brains exhibit a significant reduction of DNMBP mRNA compared with age-matched ones (P<0.0169). Thus, we confirmed the association of DNMBP with AD individuals with the APOE-epsilon3*3 genotype or lacking the epsilon4 allele, and DNMBP may be one of the susceptibility genes for AD. SN - 0964-6906 UR - https://www.unboundmedicine.com/medline/citation/16740596/Dynamin_binding_protein_gene_on_chromosome_10q_is_associated_with_late_onset_Alzheimer's_disease_ L2 - https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/ddl142 DB - PRIME DP - Unbound Medicine ER -