TY - JOUR
T1 - Association between DPP6 polymorphism and the risk of progressive multiple sclerosis in Northern and Southern Europeans
AU - Brambilla, Paola
AU - Esposito, Federica
AU - Lindstrom, Eva
AU - Sorosina, Melissa
AU - Giacalone, Giacomo
AU - Clarelli, Ferdinando
AU - Rodegher, Mariaemma
AU - Colombo, Bruno
AU - Moiola, Lucia
AU - Ghezzi, Angelo
AU - Capra, Ruggero
AU - Collimedaglia, Laura
AU - Coniglio, Gabriella
AU - Celius, Elisabeth G
AU - Galimberti, Daniela
AU - Sørensen, Per Soelberg
AU - Martinelli, Vittorio
AU - Oturai, Annette B
AU - Harbo, Hanne F
AU - Hillert, Jan
AU - Comi, Giancarlo
AU - Martinelli-Boneschi, Filippo
N1 - Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
PY - 2012/11/21
Y1 - 2012/11/21
N2 - Background: In this study, we investigated the role of the dipeptidyl-peptidase-6 (DPP6) gene in the etiopathogenesis of progressive forms of multiple sclerosis (PrMS).This gene emerged as a candidate gene in a genome-wide association study (GWAS) performed in an Italian sample of PrMS and controls in which two SNPs located in the gene (rs6956703 and rs11767658) showed evidence of association (nominal p-value<10-4) (Martinelli-Boneschi et al.) [18]. Moreover, the gene is highly expressed in the central nervous system, and it has been found to be associated with sporadic cases of amyotrophic lateral sclerosis which shares some feature with PrMS. Methods: We genotyped 19 SNPs selected using a direct and tagging approach in 244 Italian PrMS and 225 controls, and we measured the expression levels of the gene in 13 PrMS cases and 25 controls. Results: Five out of 19 SNPs were found to be associated with the disease (adjusted p<0.05), and they have been tested in an independent sample of 179 primary progressive MS and 198 controls from Northern Europe. None of the SNPs was replicated, but combined analysis confirmed the presence of association for rs2046748 (p=2.5×10-3,OR=1.82, 95%CI=1.24-2.69). Conclusions: These results, inflated by the limited sample size determined by the rarity of this condition, suggest a possible role of this gene in the susceptibility to PrMS, at least in Southern Europeans. Moreover, DPP6 was over-expressed in PrMS patients compared to controls.
AB - Background: In this study, we investigated the role of the dipeptidyl-peptidase-6 (DPP6) gene in the etiopathogenesis of progressive forms of multiple sclerosis (PrMS).This gene emerged as a candidate gene in a genome-wide association study (GWAS) performed in an Italian sample of PrMS and controls in which two SNPs located in the gene (rs6956703 and rs11767658) showed evidence of association (nominal p-value<10-4) (Martinelli-Boneschi et al.) [18]. Moreover, the gene is highly expressed in the central nervous system, and it has been found to be associated with sporadic cases of amyotrophic lateral sclerosis which shares some feature with PrMS. Methods: We genotyped 19 SNPs selected using a direct and tagging approach in 244 Italian PrMS and 225 controls, and we measured the expression levels of the gene in 13 PrMS cases and 25 controls. Results: Five out of 19 SNPs were found to be associated with the disease (adjusted p<0.05), and they have been tested in an independent sample of 179 primary progressive MS and 198 controls from Northern Europe. None of the SNPs was replicated, but combined analysis confirmed the presence of association for rs2046748 (p=2.5×10-3,OR=1.82, 95%CI=1.24-2.69). Conclusions: These results, inflated by the limited sample size determined by the rarity of this condition, suggest a possible role of this gene in the susceptibility to PrMS, at least in Southern Europeans. Moreover, DPP6 was over-expressed in PrMS patients compared to controls.
U2 - 10.1016/j.neulet.2012.10.008
DO - 10.1016/j.neulet.2012.10.008
M3 - Journal article
SN - 0167-6253
VL - 530
SP - 155
EP - 160
JO - Neuroscience letters. Supplement
JF - Neuroscience letters. Supplement
IS - 2
ER -