The RELN Locus in Alzheimer's Disease

Article type: Research Article

Authors: Seripa, Davide^{a; *} | Matera, Maria Giovanna^a | Franceschi, Marilisa^a | Daniele, Antonio^b | Bizzarro, Alessandra^b | Rinaldi, Monica^c | Panza, Francesco^d | Fazio, Vito Michele^{e; f} | Gravina, Carolina^a | D'Onofrio, Grazia^a | Solfrizzi, Vincenzo^d | Masullo, Carlo^b | Pilotto, Alberto^a

Affiliations: [a] Geriatric Unit & Gerontology-Geriatric Research Laboratory, Department of Medical Sciences, I.R.C.C.S. “Casa Sollievo dalla Sofferenza”, San Giovanni Rotondo (FG), I-71013, Italy | [b] Institute of Neurology, Catholic University School of Medicine, Rome, Italy | [c] Institute of Neurobiology and Molecular Medicine, CNR-ARTOV, Rome, Italy | [d] Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari, Bari (BA), Italy | [e] Laboratory of Oncology, I.R.C.C.S. “Casa Sollievo dalla Sofferenza”, San Giovanni Rotondo (FG), Italy | [f] Laboratory of Molecular Medicine & Biotechnology, Campus Bio-Medico University School of Medicine, Rome, Italy

Correspondence: [*] Corresponding author: Dr. Davide Seripa, Geriatric Unit & Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, I.R.C.C.S. “Casa Sollievo della Sofferenza”, Viale Cappuccini 1, San Giovanni Rotondo (FG), I-71013, Italy. Tel.: +390882416260; Fax: +390882416264; E-mail: [email protected].

Abstract: Reelin, a serine protease encoded by the RELN gene, is part of the apolipoprotein E (apoE) biochemical pathway that is involved in the pathogenesis of Alzheimer's disease (AD). Sex-related differences in the epidemiology, pathology and clinical characteristics of AD have been reported. To explore the potential contribution of RELN gene variants in the pathogenesis of AD, we investigated three polymorphisms spanning the RELN locus, i.e., a triplet tandem repeat in the 5'UTR and two single-nucleotide polymorphisms (SNPs) rs607755 and rs2229874, located in the splice-junction of exon 6 and in the coding region of exon 50. The analysis was made in 223 sporadic AD patients and 181 age-matched controls of Caucasian ethnicity. Significant differences between AD patients and controls were found in distribution of 5'UTR and rs607755 genotypes, whereas no differences were found in the distribution of rs2229874 genotypes. When patients and controls were divided according to sex, significant differences in genotype distribution were found in females and not in males, also after adjustment for APOE genotypes. These findings suggest that RELN gene variants may play a role in the pathogenesis of AD, particularly in females.

Keywords: Alzheimer's disease, apolipoprotein E, case-control studies, gene polymorphism, Reelin, RELN, risk factors, single-nucleotide polymorphism

DOI: 10.3233/JAD-2008-14308

Journal: Journal of Alzheimer's Disease, vol. 14, no. 3, pp. 335-344, 2008