1. ¹Institute of Neurology, Department of Neuroscience, Catholic University School of Medicine, Rome, Italy
2. ²Geriatric Unit and Laboratory of Gerontology-Geriatrics, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy
3. ³Institute of Medical Genetics, Catholic University School of Medicine, Rome, Italy

Correspondence: Dr A Bizzarro, Institute of Neurology, Catholic University of Sacred Heart, Largo A Gemelli 8, 00168 Roma, Italy. Tel: +39 06 3015 4435; Fax: +39 06 35501909; E-mail: alessandrabizzarro@libero.it

Received 7 May 2008; Revised 17 November 2008; Accepted 3 December 2008; Published online 28 January 2009.

Abstract

The single nucleotide polymorphisms (SNPs) rs449647, rs769446 and rs405509 in the promoter region of the APOE gene have been variously suggested to be 4-independent risk factors for Alzheimer's disease (AD). A previous Italian study found that the rs449647 was significantly associated with late-onset AD. The aim of this study was to verify whether these APOE promoter SNPs are genetic risk factors for AD and to investigate their interaction with the common APOE polymorphism. A total of 169 clinically diagnosed AD patients and 99 cognitively intact age-matched controls were included in the study. Significant associations with AD independent from sex, age and APOE/4 status were found for rs449647 A/A and rs405509 G/G genotypes (positive), and rs449647 A/T and rs405509 T/T genotypes (negative). Haplotype frequency estimation at the APOE locus showed significant associations for the ATG4, ATT4 and ACG3 (positive) and ATT2, ATT3 and TCG3 (negative) haplotypes. Therefore this study confirms the role of the rs449647 A/A genotype as risk factor for AD in Italy and suggests that promoter genotypes and APOE haplotypes might have a complex function in AD-associated genetic risk factors.