Analysis of European mitochondrial haplogroups with Alzheimer disease risk.
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.
van der Walt
Joelle M
JM
Department of Medicine, Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.
Dementieva
Yulia A
YA
Martin
Eden R
ER
Scott
William K
WK
Nicodemus
Kristin K
KK
Kroner
Charles C
CC
Welsh-Bohmer
Kathleen A
KA
Saunders
Ann M
AM
Roses
Allen D
AD
Small
Gary W
GW
Schmechel
Donald E
DE
Murali Doraiswamy
P
P
Gilbert
John R
JR
Haines
Jonathan L
JL
Vance
Jeffery M
JM
Pericak-Vance
Margaret A
MA
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
D001057:Apolipoproteins E; D004272:DNA, Mitochondrial