Analysis of European mitochondrial haplogroups with Alzheimer disease risk

• Published in: Neuroscience letters Vol. 365; no. 1; pp. 28 - 32
• Main Authors: van der Walt, Joelle M, Dementieva, Yulia A, Martin, Eden R, Scott, William K, Nicodemus, Kristin K, Kroner, Charles C, Welsh-Bohmer, Kathleen A, Saunders, Ann M, Roses, Allen D, Small, Gary W, Schmechel, Donald E, Murali Doraiswamy, P, Gilbert, John R, Haines, Jonathan L, Vance, Jeffery M, Pericak-Vance, Margaret A
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 15.07.2004; Elsevier
• Subjects: Aged; Alzheimer disease; Alzheimer Disease - genetics; APOE; Apolipoproteins E - metabolism; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA, Mitochondrial - genetics; European Continental Ancestry Group; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Haplotypes; Humans; Male; Medical sciences; Mitochondria - genetics; Mitochondrial haplogroups; mtDNA; Neurology; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Risk Factors; Sex Factors; Vertebrates: nervous system and sense organs; APOE; Alzheimer disease; mtDNA; Mitochondrial haplogroups; Nervous system diseases; Mitochondria; Apolipoprotein E; Central nervous system disease; Degenerative disease; Cerebral disorder
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2004.04.051

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.