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Article: Replication of twelve association studies for Huntington's disease residual age of onset in large Venezuelan kindreds

TitleReplication of twelve association studies for Huntington's disease residual age of onset in large Venezuelan kindreds
Authors
Issue Date2007
PublisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/
Citation
Journal Of Medical Genetics, 2007, v. 44 n. 1, p. 44-50 How to Cite?
AbstractBackground: The major determinant of age of onset in Huntington's disease is the length of the causative triplet CAG repeat. Significant variance remains, however, in residual age of onset even after repeat length is factored out. Many genetic polymorphisms have previously shown evidence of association with age of onset of Huntington's disease in several different populations. Objective: To replicate these genetic association tests in 443 affected people from a large set of kindreds from Venezuela. Methods: Previously tested polymorphisms were analysed in the HD gene itself (HD), the GluR6 kainate glutamate receptor (GRIK2), apolipoprotein E (APOE), the transcriptional coactivator CA150 (TCERG1), the ubiquitin carboxy-terminal hydrolase L1 (UCHL1), p53 (TP53), caspase-activated DNase (DFFB), and the NR2A and NR2B glutamate receptor subunits (GRIN2A, GRIN2B). Results: The GRIN2A single-nucleotide polymorphism explains a small but considerable amount of additional variance in residual age of onset in our sample. The TCERG1 microsatellite shows a trend towards association but does not reach statistical significance, perhaps because of the uninformative nature of the polymorphism caused by extreme allele frequencies. We did not replicate the genetic association of any of the other genes. Conclusions: GRIN2A and TCERG1 may show true association with residual age of onset for Huntington's disease. The most surprising negative result is for the GRIK2 (TAA)n polymorphism, which has previously shown association with age of onset in four independent populations with Huntington's disease. The lack of association in the Venezuelan kindreds may be due to the extremely low frequency of the key (TAA)16 allele in this population.
Persistent Identifierhttp://hdl.handle.net/10722/45302
ISSN
2015 Impact Factor: 5.65
2015 SCImago Journal Rankings: 3.820
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorAndresen, JMen_HK
dc.contributor.authorGayán, Jen_HK
dc.contributor.authorCherny, SSen_HK
dc.contributor.authorBrocklebank, Den_HK
dc.contributor.authorAlkortaAranburu, Gen_HK
dc.contributor.authorAddis, EAen_HK
dc.contributor.authorCardon, LRen_HK
dc.contributor.authorHousman, DEen_HK
dc.contributor.authorWexler, NSen_HK
dc.date.accessioned2007-10-30T06:22:18Z-
dc.date.available2007-10-30T06:22:18Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of Medical Genetics, 2007, v. 44 n. 1, p. 44-50en_HK
dc.identifier.issn0022-2593en_HK
dc.identifier.urihttp://hdl.handle.net/10722/45302-
dc.description.abstractBackground: The major determinant of age of onset in Huntington's disease is the length of the causative triplet CAG repeat. Significant variance remains, however, in residual age of onset even after repeat length is factored out. Many genetic polymorphisms have previously shown evidence of association with age of onset of Huntington's disease in several different populations. Objective: To replicate these genetic association tests in 443 affected people from a large set of kindreds from Venezuela. Methods: Previously tested polymorphisms were analysed in the HD gene itself (HD), the GluR6 kainate glutamate receptor (GRIK2), apolipoprotein E (APOE), the transcriptional coactivator CA150 (TCERG1), the ubiquitin carboxy-terminal hydrolase L1 (UCHL1), p53 (TP53), caspase-activated DNase (DFFB), and the NR2A and NR2B glutamate receptor subunits (GRIN2A, GRIN2B). Results: The GRIN2A single-nucleotide polymorphism explains a small but considerable amount of additional variance in residual age of onset in our sample. The TCERG1 microsatellite shows a trend towards association but does not reach statistical significance, perhaps because of the uninformative nature of the polymorphism caused by extreme allele frequencies. We did not replicate the genetic association of any of the other genes. Conclusions: GRIN2A and TCERG1 may show true association with residual age of onset for Huntington's disease. The most surprising negative result is for the GRIK2 (TAA)n polymorphism, which has previously shown association with age of onset in four independent populations with Huntington's disease. The lack of association in the Venezuelan kindreds may be due to the extremely low frequency of the key (TAA)16 allele in this population.en_HK
dc.format.extent242968 bytes-
dc.format.extent2015 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypetext/plain-
dc.languageengen_HK
dc.publisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/en_HK
dc.relation.ispartofJournal of Medical Geneticsen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsJournal of Medical Genetics. Copyright © B M J Publishing Group.en_HK
dc.subject.meshHuntington Disease - epidemiology - geneticsen_HK
dc.subject.meshPolymorphism, Single Nucleotideen_HK
dc.subject.meshReceptors, N-Methyl-D-Aspartate - geneticsen_HK
dc.subject.meshTrans-Activators - geneticsen_HK
dc.subject.meshUbiquitin Thiolesterase - geneticsen_HK
dc.titleReplication of twelve association studies for Huntington's disease residual age of onset in large Venezuelan kindredsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-2593&volume=44&issue=1&spage=44&epage=50&date=2007&atitle=Replication+of+twelve+association+studies+for+Huntington%27s+disease+residual+age+of+onset+in+large+Venezuelan+kindredsen_HK
dc.identifier.emailCherny, SS: cherny@hku.hken_HK
dc.identifier.authorityCherny, SS=rp00232en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1136/jmg.2006.045153en_HK
dc.identifier.pmid17018562-
dc.identifier.pmcidPMC2597910-
dc.identifier.scopuseid_2-s2.0-33846436448en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33846436448&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume44en_HK
dc.identifier.issue1en_HK
dc.identifier.spage44en_HK
dc.identifier.epage50en_HK
dc.identifier.eissn1468-6244-
dc.identifier.isiWOS:000243305700007-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridAndresen, JM=7103027653en_HK
dc.identifier.scopusauthoridGayán, J=6603558565en_HK
dc.identifier.scopusauthoridCherny, SS=7004670001en_HK
dc.identifier.scopusauthoridBrocklebank, D=6603151750en_HK
dc.identifier.scopusauthoridAlkortaAranburu, G=24480835200en_HK
dc.identifier.scopusauthoridAddis, EA=36942477800en_HK
dc.identifier.scopusauthoridCardon, LR=7005082964en_HK
dc.identifier.scopusauthoridHousman, DE=7102570207en_HK
dc.identifier.scopusauthoridWexler, NS=7003831887en_HK

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