{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:58:03Z","timestamp":1790485083546,"version":"4.1.0"},"reference-count":40,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:p>\n                  <jats:bold>Background:<\/jats:bold> The major determinant of age of onset in Huntington\u2019s 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\u2019s disease in several different populations.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Objective:<\/jats:bold> To replicate these genetic association tests in 443 affected people from a large set of kindreds from Venezuela.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold> Previously tested polymorphisms were analysed in the <jats:italic>HD<\/jats:italic> gene itself (<jats:italic>HD<\/jats:italic>), the GluR6 kainate glutamate receptor (<jats:italic>GRIK2<\/jats:italic>), apolipoprotein E (<jats:italic>APOE<\/jats:italic>), the transcriptional coactivator CA150 (<jats:italic>TCERG1<\/jats:italic>), the ubiquitin carboxy-terminal hydrolase L1 (<jats:italic>UCHL1<\/jats:italic>), p53 (<jats:italic>TP53<\/jats:italic>), caspase-activated DNase (<jats:italic>DFFB<\/jats:italic>), and the NR2A and NR2B glutamate receptor subunits (<jats:italic>GRIN2A<\/jats:italic>, <jats:italic>GRIN2B<\/jats:italic>).<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold> The <jats:italic>GRIN2A<\/jats:italic> single-nucleotide polymorphism explains a small but considerable amount of additional variance in residual age of onset in our sample. The <jats:italic>TCERG1<\/jats:italic> 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.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusions:<\/jats:bold>\n                  <jats:italic>GRIN2A<\/jats:italic> and <jats:italic>TCERG1<\/jats:italic> may show true association with residual age of onset for Huntington\u2019s disease. The most surprising negative result is for the <jats:italic>GRIK2<\/jats:italic> (TAA)<jats:sub>n<\/jats:sub> polymorphism, which has previously shown association with age of onset in four independent populations with Huntington\u2019s disease. The lack of association in the Venezuelan kindreds may be due to the extremely low frequency of the key (TAA)<jats:sub>16<\/jats:sub> allele in this population.<\/jats:p>","DOI":"10.1136\/jmg.2006.045153","type":"journal-article","created":{"date-parts":[[2006,10,3]],"date-time":"2006-10-03T22:05:39Z","timestamp":1159913139000},"page":"44-50","source":"Crossref","is-referenced-by-count":71,"title":["Replication of twelve association studies for Huntington\u2019s disease residual age of onset in large Venezuelan kindreds"],"prefix":"10.1136","volume":"44","author":[{"given":"J M","family":"Andresen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Gay\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S S","family":"Cherny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Brocklebank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Alkorta-Aranburu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E A","family":"Addis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L R","family":"Cardon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D E","family":"Housman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N S","family":"Wexler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2006,10,3]]},"reference":[{"key":"2025100520584773000_44.1.44.1","unstructured":"Bates G , Harper P, Jones L. 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