TY - JOUR
T1 - Implication of common and disease specific variants in CLU, CR1, and PICALM
AU - Ferrari, Raffaele
AU - Moreno, Jorge H.
AU - Minhajuddin, Abu T.
AU - O'Bryant, Sid E.
AU - Reisch, Joan S.
AU - Barber, Robert C.
AU - Momeni, Parastoo
N1 - Funding Information:
The authors thank the Investigators from the Texas Alzheimer's Research Consortium: Baylor College of Medicine: Susan Rountree, Eveleen Darby, Aline Hittle, Aisha Khaleeg; Texas Tech University Health Science Center (TTUHSC): Benjamin Williams, Andrew Dentino, Gregory Schrimsher, Larry Hill; University of North Texas Health Science Center: Janice Knebl, Lisa Alvarez, Douglas Mains, Thomas Fairchild, James Hall; University of Texas Southwestern Medical Center: Perrie Adams, Roger Rosenberg, Ryan Huebinger, Janet Smith, Mechelle Murray, Tomequa Sears. Not least, the authors thank Mr. Poorna Dharmasri for helping in critical reading and editing this manuscript. The molecular genetic study in Dr. Momeni's laboratory and this work was supported by the financial and administrative support from the Office of the Dean and Department of Internal Medicine at TTUHSC. The collection of samples and the corresponding clinical data for this study was made possible by the Texas Alzheimer's Research and Care Consortium (TARCC) funded by the state of Texas through the Texas Council on Alzheimer's Disease and Related Disorders.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2012/8
Y1 - 2012/8
N2 - Two recent genome-wide association studies (GWAS) for late onset Alzheimer's disease (LOAD) revealed 3 new genes: clusterin (CLU), phosphatidylinositol binding clathrin assembly protein (PICALM), and complement receptor 1 (CR1). In order to evaluate association with these genome-wide association study-identified genes and to isolate the variants contributing to the pathogenesis of LOAD, we genotyped the top single nucleotide polymorphisms (SNPs), rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), and sequenced the entire coding regions of these genes in our cohort of 342 LOAD patients and 277 control subjects. We confirmed the association of rs3851179 (PICALM) (p = 7.4 × 10-3) with the disease status. Through sequencing we identified 18 variants in CLU, 3 of which were found exclusively in patients; 8 variants (out of 65) in CR1 gene were only found in patients and the 16 variants identified in PICALM gene were present in both patients and controls. In silico analysis of the variants in PICALM did not predict any damaging effect on the protein. The haplotype analysis of the variants in each gene predicted a common haplotype when the 3 single nucleotide polymorphisms rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), respectively, were included. For each gene the haplotype structure and size differed between patients and controls. In conclusion, we confirmed association of CLU, CR1, and PICALM genes with the disease status in our cohort through identification of a number of disease-specific variants among patients through the sequencing of the coding region of these genes.
AB - Two recent genome-wide association studies (GWAS) for late onset Alzheimer's disease (LOAD) revealed 3 new genes: clusterin (CLU), phosphatidylinositol binding clathrin assembly protein (PICALM), and complement receptor 1 (CR1). In order to evaluate association with these genome-wide association study-identified genes and to isolate the variants contributing to the pathogenesis of LOAD, we genotyped the top single nucleotide polymorphisms (SNPs), rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), and sequenced the entire coding regions of these genes in our cohort of 342 LOAD patients and 277 control subjects. We confirmed the association of rs3851179 (PICALM) (p = 7.4 × 10-3) with the disease status. Through sequencing we identified 18 variants in CLU, 3 of which were found exclusively in patients; 8 variants (out of 65) in CR1 gene were only found in patients and the 16 variants identified in PICALM gene were present in both patients and controls. In silico analysis of the variants in PICALM did not predict any damaging effect on the protein. The haplotype analysis of the variants in each gene predicted a common haplotype when the 3 single nucleotide polymorphisms rs11136000 (CLU), rs3818361 (CR1), and rs3851179 (PICALM), respectively, were included. For each gene the haplotype structure and size differed between patients and controls. In conclusion, we confirmed association of CLU, CR1, and PICALM genes with the disease status in our cohort through identification of a number of disease-specific variants among patients through the sequencing of the coding region of these genes.
KW - Alzheimer's disease (AD)
KW - Clusterin (CLU)
KW - Complement receptor 1 (CR1)
KW - Genome wide association study (GWAS)
KW - Phosphotidylinositol binding clathrin assembly protein (PICALM)
UR - http://www.scopus.com/inward/record.url?scp=84861875043&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2012.01.110
DO - 10.1016/j.neurobiolaging.2012.01.110
M3 - Article
C2 - 22402018
AN - SCOPUS:84861875043
SN - 0197-4580
VL - 33
SP - 1846.e7-1846.e18
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 8
ER -