Mitochondrial haplogroup H and Alzheimer's disease—Is there a connection?

Maruszak, Aleksandra; Canter, Jeffrey A; Styczyńska, Maria; Żekanowski, Cezary; Barcikowska, Maria

doi:10.1016/j.neurobiolaging.2008.01.004

« Previous Next »Neurobiology of Aging
Volume 30, Issue 11 , Pages 1749-1755, November 2009

Mitochondrial haplogroup H and Alzheimer's disease—Is there a connection?

Aleksandra Maruszak
- Department of Neurodegenerative Disorders, Polish Academy of Sciences Medical Research Center, 5 Pawińskiego Street, 02-106 Warsaw, Poland
- Corresponding author. Tel.: +48 22 6086485; fax: +48 22 6685532.
Jeffrey A Canter
- Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA
Maria Styczyńska
- Department of Neurodegenerative Disorders, Polish Academy of Sciences Medical Research Center, 5 Pawińskiego Street, 02-106 Warsaw, Poland
Cezary Żekanowski
- Department of Neurodegenerative Disorders, Polish Academy of Sciences Medical Research Center, 5 Pawińskiego Street, 02-106 Warsaw, Poland
Maria Barcikowska
- Department of Neurodegenerative Disorders, Polish Academy of Sciences Medical Research Center, 5 Pawińskiego Street, 02-106 Warsaw, Poland

Received 7 August 2007; received in revised form 5 December 2007; accepted 5 January 2008. published online 29 February 2008.

Abstract

We evaluated the involvement of the major Caucasian-specific mitochondrial haplogroups (H, I, J, K, T, U, V, W and X), haplogroup clusters (HV, UK, TJ, IWX) and two functional mtSNPs (4216, 4917) in the pathogenesis of Alzheimer's disease (AD) in the Polish population. The frequency distribution of mtDNA haplogroups was non-randomly associated with APOE4 status (χ²=73.17, df=1, p<0.0001, OR=5.97, 95% CI 3.90–9.12), however, no haplogroup-specific neutralizing of the APOE4 allele influence was detected. Multivariate analysis suggested the opposite—APOE4 status could modulate the effect of mtDNA haplogroups.

We found that HV cluster is significantly associated with the risk of AD, regardless of the APOE4 status (OR=1.59, 95% CI, 1.04–2.44, p=0.032). Contrary to the previous studies, we report no evidence for the involvement of haplogroup U, K, J or T in AD risk. We conclude that further analysis of subtypes of haplogroup H would be necessary to decipher the relation of HV cluster with AD.

Keywords: Alzheimer's disease, Mitochondrial haplogroup, Mitochondrial DNA, APOE4, Polymorphism