{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T04:13:14Z","timestamp":1769746394422,"version":"3.49.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Interleukin-1\u03b2 (IL-1\u03b2) is a potent stimulator of bone resorption, and has been implicated in the pathogenesis of high bone turnover and osteoporosis. IL-1 receptor antagonist (IL-1ra) is a competitive inhibitor of IL-1\u03b2 effects and the biological effects of IL-1\u03b2 are therefore proportional to the ratio IL-1\u03b2\/IL-1ra. The coding regions of IL-1\u03b2 were examined for sequence variations by SSCP and sequencing after polymerase chain reaction (PCR) of genomic DNA. Three previously described polymorphisms (C\u2212511-T, G3877-A and C3954-T) in the IL-1\u03b2 gene were determined by restriction fragment length polymorphism (RFLP) using Ava I, Aci I, and Taq I after PCR. The 86-base pair repeat polymorphism in IL-1ra was examined by PCR and electrophoresis and the T11100-C polymorphism in the IL-1ra gene was examined by RFLP using MspA1I after PCR. All polymorphisms were related to bone mass, biochemical markers of bone turnover, and presence of fracture in a study including 389 osteoporotic patients with vertebral fractures and normal controls. Two normal women were heterozygous for a shift from cytosine to thymine (C3263-T) in exon 4 of the IL-1\u03b2 gene. This substitution did not affect the amino acid sequence. We did not find other sequence variations in the IL-1\u03b2 gene apart from the already known polymorphisms. The distribution of C\u2212511-T, G3877-A, and C3954-T genotypes was similar in the osteoporotic and the normal controls. No significant differences could be shown in bone mass or bone turnover. In the IL-1ra gene almost complete linkage was confirmed between the already known polymorphisms: G1731-A, G1821-A, A1868-G, G1887-C, T8006-C, C8061-T, 86 base pair variable number tandem repeat (VNTR), A9589-T, and a new polymorphism: T1934-C. The A1A1\/A3 genotypes of the IL-1ra VNTR polymorphism were significantly more frequent in osteoporotic patients (56.2%) compared with age-matched normal controls (433%) (\u03c72 = 4.09; p = 0.043). The relative risk of osteoporotic fractures was increased to 1.68 (95% CI, 1.01\u20132.77) in individuals with A1A1\/A3 genotypes. Bone mineral density (BMD) of the lumbar spine was reduced in individuals with A1A1\/A3 genotypes (p = 0.014, analysis of variance [ANOVA]). The difference in bone mass between A1A1\/A3 and A2A1\/A2 tended to increase with increasing age. T11100-C genotypes were distributed similarly in osteoporotic patients and normal controls and the polymorphism was without effect on bone mass and biochemical markers of bone turnover. In conclusion, an 86-base pair repeat polymorphism in the IL-1ra gene is associated with increased risk of osteoporotic fractures. Other polymorphisms in the IL-1ra and the IL-1\u03b2 genes are not associated with osteoporotic fractures or alterations in bone mass or bone turnover.<\/jats:p>","DOI":"10.1359\/jbmr.2000.15.3.402","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T02:14:02Z","timestamp":1146104042000},"page":"402-414","source":"Crossref","is-referenced-by-count":84,"title":["Osteoporotic Fractures Are Associated with an 86-Base Pair Repeat Polymorphism in the Interleukin-1-Receptor Antagonist Gene But Not with Polymorphisms in the Interleukin-1\u03b2 Gene"],"prefix":"10.1093","volume":"15","author":[{"given":"Bente L.","family":"Langdahl","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus Amtssygehus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elsebet","family":"L\u00f8kke","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus Amtssygehus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mette","family":"Carstens","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus Amtssygehus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lise Lotte","family":"Stenkj\u00e6r","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus Amtssygehus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik Fink","family":"Eriksen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus Amtssygehus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,2,18]]},"reference":[{"key":"2024020714104474800_bib1","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1172\/JCI113125","article-title":"Genetic deteminants of bone mass in adults. 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