title: Analysis of European mitochondrial haplogroups with Alzheimer disease risk.
abstract: We examined the association of mtDNA variation with Alzheimer disease (AD) risk in Caucasians (989 cases and 328 controls) testing the effect of individual haplogroups and single nucleotide polymorphisms (SNPs). Logistic regression analyses were used to assess risk of haplogroups and SNPs with AD in both main effects and interaction models. Males classified as haplogroup U showed an increase in risk (OR = 2.30; 95% CI, 1.03-5.11; P = 0.04) of AD relative to the most common haplogroup H, while females demonstrated a significant decrease in risk with haplogroup U (OR = 0.44 ; 95% CI, 0.24-0.80; P = 0.007). Our results were independent of APOE genotype, demonstrating that the effect of mt variation is not confounded by APOE4 carrier status. We suggest that variations within haplogroup U may be involved in AD expression in combination with environmental exposures or nuclear proteins other than APOE.
authors.affiliation: Department of Medicine, Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Joelle M
authors.initials: JM
authors.lastname: van der Walt
authors.forename: Yulia A
authors.initials: YA
authors.lastname: Dementieva
authors.forename: Eden R
authors.initials: ER
authors.lastname: Martin
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Nicodemus
authors.forename: Charles C
authors.initials: CC
authors.lastname: Kroner
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Welsh-Bohmer
authors.forename: Ann M
authors.initials: AM
authors.lastname: Saunders
authors.forename: Allen D
authors.initials: AD
authors.lastname: Roses
authors.forename: Gary W
authors.initials: GW
authors.lastname: Small
authors.forename: Donald E
authors.initials: DE
authors.lastname: Schmechel
authors.forename: P
authors.initials: P
authors.lastname: Murali Doraiswamy
authors.forename: John R
authors.initials: JR
authors.lastname: Gilbert
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Vance
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D044465:White People
chemical_list: D001057:Apolipoproteins E; D004272:DNA, Mitochondrial