title: Candidate gene association study of solute carrier family 11a members 1 (SLC11A1) and 2 (SLC11A2) genes in Alzheimer's disease.
abstract: Divalent cations are strongly implicated in Alzheimer's disease (AD) pathogenesis, and can regulate amyloid beta-peptide aggregation. The proton-divalent cation transporters encoded by SLC11A1 (formerly NRAMP1) on chromosome 2q35, and SLC11A2 (also known as DCT1 and DMT1) on chromosome 12q13, are expressed in the brain and regulate ion homeostasis from endosomal compartments. SLC11A1 also has pleiotropic effects on pro-inflammatory responses that may be important in AD. We analyzed seven informative polymorphisms in the SLC11A1 and SLC11A2 genes encoding these divalent cation transporters in a sample of 216 late-onset AD cases and 323 age-matched controls. We found only borderline evidence (p=0.08) for an allelic association between SNP rs407135 at SLC11A2 and AD, in which the variant allele was protective (odd ratio (OR) 0.77; 95% CI 0.56-1.04) relative to the more common allele. There was no interaction with apolipoprotein E (APOE) varepsilon4, but stratification by gender showed that all of the effect of SLC11A2 was in the male patient group. No other associations with AD were observed at SLC11A1 or SLC11A2, indicating no major effect of either gene for the occurrence of AD.
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Rd., Cambridge CB2 2XY, UK.
authors.forename: Sarra E
authors.initials: SE
authors.lastname: Jamieson
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: White
authors.forename: Joanna M M
authors.initials: JM
authors.lastname: Howson
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pask
authors.forename: Anne N
authors.initials: AN
authors.lastname: Smith
authors.forename: Carol
authors.initials: C
authors.lastname: Brayne
authors.forename: John Grimley
authors.initials: JG
authors.lastname: Evans
authors.forename: John
authors.initials: J
authors.lastname: Xuereb
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.forename: David C
authors.initials: DC
authors.lastname: Rubinsztein
authors.forename: Jenefer M
authors.initials: JM
authors.lastname: Blackwell
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012737:Sex Factors; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D001057:Apolipoproteins E; D027682:Cation Transport Proteins; D033862:Iron-Binding Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2