Analysis of chromosome 12 candidate genes in late-onset Alzheimer disease

Janet M. Grubber, Ann M. Saunders, Larry H. Yamaoka, William K. Scott, Eden R. Martin, De'Lisa M. Hill, Claire L. Standen, P. Michael Conneally, Gary W. Small, Eric H. Lai, John R. Gilbert, Allen D. Roses, Jonathan L. Haines, Margaret A. Pericak-Vance

Research output: Contribution to journalArticlepeer-review

Abstract

Three Alzheimer disease (AD) causing genes : amyloid precursor protein , presenilin 1 , and presenilin 2 ; and one susceptibility gene , apolipoprotein E , have been identified . Jointly these genes account for approximately 50% of the total genetic effect on AD risk , leaving 50% of the genetic effect unexplained . Studies indicate that one of the most promising locations for a fifth AD gene is the centromeric region of chromosome 12 . This chromosomal region contains several genes that are potential candidates for the chromosome 12 AD gene . The Pedigree Disequilibrium Test (PDT) was used to test for allelic association and linkage between AD and nine chromosome 12 candidate genes in a series of multiplex ( 2 AD individuals/family) AD families as diagnosed by NINCDS-ADRDA criteria . The genes examined were the neurotrophin-3 (NTF3) ; tumor necrosis factor receptor 1 (TNFR1) ; human complement component (C1R) ; oxidized low-density lipoprotein receptor (OLR1 ) ; islet amyloid polypeptide (IAPP) ; Kirsten rat sarcom 2 viral oncogene (KRAS2) ; mitochondrial ATP synthase , ; subunit (ATP5B) ; human brain sodium channel 2 (hBNaC2) ; and interleukin-4 Stat (IL-4 Stat) . These genes are located in an approximately 65 cM region spanning 12p13 to 12q13 . PDT p-values were not statistically significant for any of the candidate genes tested , ranging from 0 .23 (IAPP) to 0 .94 (KRAS2) . These data provide no evidence that any of the candidate genes examined here is the sought after chromosome 12 AD susceptibility gene .

Original languageEnglish (US)
Pages (from-to)221-226
Number of pages6
JournalAlzheimer's Reports
Volume3
Issue number4
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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