{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T11:44:06Z","timestamp":1775303046920,"version":"3.50.1"},"reference-count":33,"publisher":"BMJ","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:p>\n                  <jats:bold>Background:<\/jats:bold> Osteoporosis, mainly characterised by low bone mineral density (BMD), is a serious public health problem. The collagen type I alpha 1 (<jats:italic>COL1A1<\/jats:italic>) gene is a prominent candidate gene for osteoporosis. Here, we examined whether genetic variants at the <jats:italic>COL1A1<\/jats:italic> gene can influence BMD variation.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold> BMD was measured at nine skeletal sites in 313 Caucasian males and 308 Caucasian females. We screened four single nucleotide polymorphisms (SNPs) at the <jats:italic>COL1A1<\/jats:italic> gene: PCOL2 (-1997 G\/T) in the promoter, Sp1 (1546 G\/T) in the intron 1, Gly19Cys (3911 G\/A) in exon 8, and Ala897Thr (13 773 G\/A) in exon 45. Univariate and multivariate association approaches were used in the analyses.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold> In multivariate analyses, we found a strong association between the PCOL2 SNP and BMD (p\u200a=\u200a0.007 to 0.024) and a suggestive association between the Sp1 SNP and BMD (p\u200a=\u200a0.023 to 0.048) in elderly Caucasian females. Interestingly, the interaction of these two SNPs was highly significantly associated with BMD variation (p\u200a=\u200a0.001 to 0.003). The haplotype <jats:italic>GG<\/jats:italic> at the two SNPs had, on average, 2.7% higher BMD than non-carriers (p\u200a=\u200a0.006 to 0.026).<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusions:<\/jats:bold> Our data suggested that the common genetic variants at the PCOL2 and Sp1 sites, and importantly, their interactive effects, may contribute to BMD variation in elderly Caucasian females. Further studies are necessary to delineate the mechanisms underlying the effects of these common variants on BMD variation and to test their clinical relevance for general populations. In addition, our study highlighted the importance of multivariate analyses when multiple correlated phenotypes are under study.<\/jats:p>","DOI":"10.1136\/jmg.2004.019851","type":"journal-article","created":{"date-parts":[[2004,10,1]],"date-time":"2004-10-01T12:24:04Z","timestamp":1096633444000},"page":"752-757","source":"Crossref","is-referenced-by-count":39,"title":["Common variants at the PCOL2 and Sp1 binding sites of the <i>COL1A1<\/i> gene and their interactive effect influence bone mineral density in Caucasians"],"prefix":"10.1136","volume":"41","author":[{"given":"P-Y","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J-R","family":"Long","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F-H","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R R","family":"Recker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H-W","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2004,10,1]]},"reference":[{"key":"2025101800563303000_41.10.752.1","first-page":"1S","volume":"95","year":"1993","journal-title":"Am J Med"},{"key":"2025101800563303000_41.10.752.2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1096-203"},{"key":"2025101800563303000_41.10.752.3","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(90)90235-X"},{"key":"2025101800563303000_41.10.752.4","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1172\/JCI10347","volume":"107","year":"2001","journal-title":"J Clin Invest"},{"key":"2025101800563303000_41.10.752.5","doi-asserted-by":"publisher","DOI":"10.1007\/s002230001160"},{"key":"2025101800563303000_41.10.752.6","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1430261"},{"key":"2025101800563303000_41.10.752.7","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005842"},{"key":"2025101800563303000_41.10.752.8","doi-asserted-by":"publisher","DOI":"10.1007\/s001980050157"},{"key":"2025101800563303000_41.10.752.9","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(03)00087-5"},{"key":"2025101800563303000_41.10.752.10","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.9.1634"},{"key":"2025101800563303000_41.10.752.11","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.7.1273"},{"key":"2025101800563303000_41.10.752.12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199804093381502"},{"key":"2025101800563303000_41.10.752.13","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1998.13.5.813"},{"key":"2025101800563303000_41.10.752.14","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1770147"},{"key":"2025101800563303000_41.10.752.15","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.4.678"},{"key":"2025101800563303000_41.10.752.16","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1002\/jbmr.5650091002","volume":"9","year":"1994","journal-title":"J Bone Miner Res"},{"key":"2025101800563303000_41.10.752.17","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.10.1965"},{"key":"2025101800563303000_41.10.752.18","first-page":"30","volume":"18","year":"1998","journal-title":"J Craniofac Genet Dev Biol"},{"key":"2025101800563303000_41.10.752.19","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.3.384"},{"key":"2025101800563303000_41.10.752.20","doi-asserted-by":"publisher","DOI":"10.1086\/301904"},{"key":"2025101800563303000_41.10.752.21","unstructured":"Merlter CA, Vannatta RA. Advanced and multivariate statistical methods: practical application and interpretation. Los Angeles: Pyrczak, 2001."},{"key":"2025101800563303000_41.10.752.22","doi-asserted-by":"publisher","DOI":"10.1017\/S0003480001008958"},{"key":"2025101800563303000_41.10.752.23","doi-asserted-by":"publisher","DOI":"10.1385\/JCD:2:3:251"},{"key":"2025101800563303000_41.10.752.24","first-page":"155","volume":"71","year":"1999","journal-title":"Hum Biol"},{"key":"2025101800563303000_41.10.752.25","first-page":"S236","volume":"17","year":"2002","journal-title":"J Bone Miner Res"},{"key":"2025101800563303000_41.10.752.26","doi-asserted-by":"publisher","DOI":"10.2307\/2533057"},{"key":"2025101800563303000_41.10.752.27","first-page":"1347","volume":"58","year":"1996","journal-title":"Am J Hum Genet"},{"key":"2025101800563303000_41.10.752.28","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/genetics\/49.1.49","volume":"49","year":"1964","journal-title":"Genetics"},{"key":"2025101800563303000_41.10.752.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.24.8869"},{"key":"2025101800563303000_41.10.752.30","unstructured":"Tabachnic BG, Fidell LS. Using multivariate statistics. New York: Harper Collins, 1996."},{"key":"2025101800563303000_41.10.752.31","doi-asserted-by":"crossref","unstructured":"Huang QY, Xu FH, Shen H, Deng HY, Conway T, Liu YJ, Liu YZ, Li JL, Li MX, Davies KM, Recker RR, Deng HW. Genome scan for QTLs underlying bone size variation at ten refined skeletal sites: genetic heterogeneity and the significance of phenotype refinement. Physiol Genomics 2004; in press. Epub ahead of print: PubMed ID 15039485.","DOI":"10.1152\/physiolgenomics.00161.2002"},{"key":"2025101800563303000_41.10.752.32","doi-asserted-by":"publisher","DOI":"10.1086\/341719"},{"key":"2025101800563303000_41.10.752.33","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.12.918"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.2004.019851","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T07:56:37Z","timestamp":1760774197000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.2004.019851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,10]]},"references-count":33,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2004,10,1]]},"published-print":{"date-parts":[[2004,10]]}},"alternative-id":["10.1136\/jmg.2004.019851"],"URL":"https:\/\/doi.org\/10.1136\/jmg.2004.019851","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,10]]}}}