{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T21:51:19Z","timestamp":1775080279127,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2003,3,1]],"date-time":"2003-03-01T00:00:00Z","timestamp":1046476800000},"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":[[2003,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Osteoporosis, a multifactorial common disease, is believed to result from the interplay of multiple environmental and genetic determinants, including factors that regulate bone mineral density. Interleukin-1 (IL-1) is one of the most potent bone-resorbing factors, and interleukin-1-associated kinase 1 (IRAK1) is an essential effector of the IL-1 receptor signaling cascade. In genetic studies of two independent populations of postmenopausal women (cohort A: 220 individuals and cohort T: 126 individuals) from separated geographical regions of Japan, we found that radial bone mineral density levels had similar associations with IRAK1 genotypes in both populations. Two amino acid-substituting variations in the gene, encoding Phe196Ser and Ser532Leu, were in complete linkage disequilibrium (D\u2032 = 1.0000, r2 = 1.0000, \u03c72 = 192.000, p = 1.2 \u00d7 10\u221243), and we found two exclusive haplotypes (196F\/532S, frequency 0.74; 196S\/532L, frequency 0.26) of the IRAK1 gene among our test subjects. In both populations, a significant association with decreased radial bone mineral density was identified with haplotype 196F\/532S (in cohort A: r = 0.21, p = 0.0017; in cohort T: r = 0.23, p = 0.011). Radial bone mineral density was lowest among 196F\/532S homozygotes, highest among 196S\/532L homozygotes, and intermediate among heterozygotes. Accelerated bone loss also correlated with the 196F\/532S haplotype in a 5-year follow-up. These results suggest that variation of IRAK1 may be an important determinant of postmenopausal osteoporosis, in part through the mechanism of accelerated postmenopausal bone loss.<\/jats:p>","DOI":"10.1359\/jbmr.2003.18.3.419","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T05:20:02Z","timestamp":1146115202000},"page":"419-423","source":"Crossref","is-referenced-by-count":22,"title":["Association of a Haplotype (196Phe\/532Ser) in the Interleukin-1-Receptor-Associated Kinase (<i>IRAK1<\/i>) Gene With Low Radial Bone Mineral Density in Two Independent Populations"],"prefix":"10.1093","volume":"18","author":[{"given":"Ryota","family":"Ishida","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Nippon Medical School, Kawasaki, Japan"},{"name":"Department of Molecular Biology, Institute of Gerontology, Kawasaki, 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