{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:36:47Z","timestamp":1789205807455,"version":"build-2803163510"},"reference-count":31,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Primary open angle glaucoma is a progressive optic neuropathy characterised by the selective loss of retinal ganglion cells, pathological optic disc cupping and visual field defects. The <jats:italic>OPA1<\/jats:italic> gene encodes an inner mitochondrial membrane protein crucial for normal mitochondrial function, and pathogenic mutations cause autosomal dominant optic atrophy by specifically targeting retinal ganglion cells. This raises the distinct possibility that more subtle genetic variations in <jats:italic>OPA1<\/jats:italic> could alter the risk of developing glaucoma.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>137 patients with primary open angle glaucoma (67 patients with high-tension glaucoma (HTG), 70 patients with normal-tension glaucoma (NTG)) and 75 controls from the North East of England were studied. Three single-nucleotide polymorphisms in intron 8 (IVS8+4c\u2192t and IVS8+32t\u2192c) and exon 4 (c.473A\u2192G) of the <jats:italic>OPA1<\/jats:italic> gene were genotyped in the study group. In addition, the entire <jats:italic>OPA1<\/jats:italic> coding region was sequenced in 24 individuals with the CT\/TT compound genotype using standard BigDye chemistries.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>There was no difference in either allele or genotype frequency for the IVS8+32t\u2192c single-nucleotide polymorphisms between patients and controls, but there was a significant association between the T allele at IVS8+4c\u2192t and the risk of developing NTG (OR=2.04, 95% CI=1.10 to 3.81, p=0.004), but not HTG. Logistic regression analysis also confirmed a strong association between the CT\/TT compound genotype at IVS8+4 and IVS8+32 with NTG (OR=29.75, 95% CI=3.83 to 231.21, p=0.001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The CT\/TT compound genotype at IVS8+4 and IVS8+32 is a strong genetic risk determinant for NTG but not HTG.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2009.067512","type":"journal-article","created":{"date-parts":[[2009,7,6]],"date-time":"2009-07-06T20:13:23Z","timestamp":1246911203000},"page":"120-125","source":"Crossref","is-referenced-by-count":53,"title":["<i>OPA1<\/i> increases the risk of normal but not high tension glaucoma"],"prefix":"10.1136","volume":"47","author":[{"given":"P","family":"Yu-Wai-Man","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J D","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R M","family":"Andrews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P G","family":"Griffiths","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M K","family":"Birch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P F","family":"Chinnery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2009,7,5]]},"reference":[{"key":"2025100511440047000_47.2.120.1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-6-58"},{"key":"2025100511440047000_47.2.120.2","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2005.081224"},{"key":"2025100511440047000_47.2.120.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-9071.2006.01268.x"},{"key":"2025100511440047000_47.2.120.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2007.08.032"},{"key":"2025100511440047000_47.2.120.5","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.125.1.30"},{"key":"2025100511440047000_47.2.120.6","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.59.4.211"},{"key":"2025100511440047000_47.2.120.7","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1977.04450040064007"},{"key":"2025100511440047000_47.2.120.8","doi-asserted-by":"publisher","DOI":"10.3109\/09286589409047221"},{"key":"2025100511440047000_47.2.120.9","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1639"},{"key":"2025100511440047000_47.2.120.10","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.054270"},{"key":"2025100511440047000_47.2.120.11","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-001-0645-7"},{"key":"2025100511440047000_47.2.120.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0711-9"},{"key":"2025100511440047000_47.2.120.13","first-page":"460","article-title":"Polymorphisms in OPA1 are associated with normal tension glaucoma","volume":"9","author":"Powell","year":"2003","journal-title":"Mol Vis"},{"key":"2025100511440047000_47.2.120.14","first-page":"1124","article-title":"Lack of association between normal-tension glaucoma and intron 8 polymorphisms in the gene causing autosomal dominant optic atrophy, OPA1, in Japan","volume":"44","author":"Sato","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2025100511440047000_47.2.120.15","doi-asserted-by":"publisher","DOI":"10.1097\/01.ijg.0000137870.25779.40"},{"key":"2025100511440047000_47.2.120.16","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.122.2.258"},{"key":"2025100511440047000_47.2.120.17","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.016089"},{"key":"2025100511440047000_47.2.120.18","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2005.084335"},{"key":"2025100511440047000_47.2.120.19","unstructured":"Bland M . 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