BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a CAG triplet repeat tract in the huntingtin gene. While the length of this CAG expansion is the major determinant of the age of onset (AO), other genetic factors have also been shown to play a modulatory role. Recent evidence suggests that neuroinflammations is a pivotal factor in the pathogenesis of HD, and that targeting this process may have important therapeutic ramifications. The human ??-defensin 2 (hBD2)- encoded by DEFB4- is an antimicrobial peptide that exhibits inducible expression in astrocytes during inflammation and is an important regulator of innate and adaptive immune response. Therefore, DEFB4 may contribute to the neuroinflammatory processes observed in HD. OBJECTIVE: In this study we tested the hypothesis that copy number variation (CNV) of the ??-defensin region, including DEFB4, modifies the AO in HD. METHODS AND RESULTS: We genotyped ??-defensin CNV in 490 HD individuals using the paralogue ratio test and found no association between ??-defensin CNV and onset of HD. CONCLUSIONS: We conclude that it is unlikely that DEFB4 plays a role in HD pathogenesis.

Beta-Defensin genomic copy number does not influence the age of onset in Huntington's Disease / Vittori, A; Orth, M; Roos, Ra; Outeiro, Tf; Giorgini, F; Hollox, Ej; Registry investigators of the European Huntington's Disease, Network; Registry investigators of the European Huntington's Disease, Network; Registry investigators of the European Huntington's Disease, N. e. t. w. o. r. k.; Salvatore, Elena; DE MICHELE, Giuseppe; Rinaldi, Carlo. - In: JOURNAL OF HUNTINGTON’S DISEASE. - ISSN 1879-6397. - 2:1(2013), pp. 107-124.

Beta-Defensin genomic copy number does not influence the age of onset in Huntington's Disease.

SALVATORE, ELENA;DE MICHELE, GIUSEPPE;RINALDI, CARLO
2013

Abstract

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a CAG triplet repeat tract in the huntingtin gene. While the length of this CAG expansion is the major determinant of the age of onset (AO), other genetic factors have also been shown to play a modulatory role. Recent evidence suggests that neuroinflammations is a pivotal factor in the pathogenesis of HD, and that targeting this process may have important therapeutic ramifications. The human ??-defensin 2 (hBD2)- encoded by DEFB4- is an antimicrobial peptide that exhibits inducible expression in astrocytes during inflammation and is an important regulator of innate and adaptive immune response. Therefore, DEFB4 may contribute to the neuroinflammatory processes observed in HD. OBJECTIVE: In this study we tested the hypothesis that copy number variation (CNV) of the ??-defensin region, including DEFB4, modifies the AO in HD. METHODS AND RESULTS: We genotyped ??-defensin CNV in 490 HD individuals using the paralogue ratio test and found no association between ??-defensin CNV and onset of HD. CONCLUSIONS: We conclude that it is unlikely that DEFB4 plays a role in HD pathogenesis.
2013
Beta-Defensin genomic copy number does not influence the age of onset in Huntington's Disease / Vittori, A; Orth, M; Roos, Ra; Outeiro, Tf; Giorgini, F; Hollox, Ej; Registry investigators of the European Huntington's Disease, Network; Registry investigators of the European Huntington's Disease, Network; Registry investigators of the European Huntington's Disease, N. e. t. w. o. r. k.; Salvatore, Elena; DE MICHELE, Giuseppe; Rinaldi, Carlo. - In: JOURNAL OF HUNTINGTON’S DISEASE. - ISSN 1879-6397. - 2:1(2013), pp. 107-124.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/597951
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