{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:00:31Z","timestamp":1784757631080,"version":"3.55.0"},"reference-count":70,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,4,2]],"date-time":"2014-04-02T00:00:00Z","timestamp":1396396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Genetic markers associated with disease are often non\u2010functional and generally tag one or more functional \u201ccausative\u201d variants in linkage disequilibrium. Markers may not show tight linkage to the causative variants across multiple ethnicities due to evolutionary divergence, and therefore may not be informative across different population groups. Validated markers of disease suggest causative variants exist in the gene and, if the causative variants can be identified, it is reasonable to hypothesize that such variants will be informative across diverse populations. The aim of this study was to test that hypothesis using functional Interleukin\u20101 (IL\u20101) gene variations across multiple ethnic populations to replace the non\u2010functional markers originally associated with chronic adult periodontitis in Caucasians.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Adult chronic periodontitis cases and controls from four ethnic groups (Caucasians, African Americans, Hispanics and Asians) were recruited in the USA, Chile and China. Genotypes of <jats:italic><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>1B<\/jats:italic> gene single nucleotide polymorphisms (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s), including three functional <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s (rs16944, rs1143623, rs4848306) in the promoter and one intronic <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content> (rs1143633), were determined using a single base extension method or TaqMan 5\u2032 nuclease assay. Logistic regression and other statistical analyses were used to examine the association between moderate to severe periodontitis and <jats:italic><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>1B<\/jats:italic> gene variations, including <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s, haplotypes and composite genotypes. Genotype patterns associated with disease in the discovery study were then evaluated in independent validation studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant associations were identified in the discovery study, consisting of Caucasians and African Americans, between moderate to severe adult chronic periodontitis and functional variations in the <jats:italic><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>1B<\/jats:italic> gene, including a pattern of four <jats:italic><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>1B <\/jats:italic><jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a01.87, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0001). The association between the disease and this <jats:italic><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>1B<\/jats:italic> composite genotype pattern was validated in two additional studies consisting of Hispanics (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a01.95, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.04) or Asians (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a03.27, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.01). A meta\u2010analysis of the three populations supported the association between the <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101 genotype pattern and moderate to severe periodontitis (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 1.95; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001). Our analysis also demonstrated that <jats:italic><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>1B<\/jats:italic> gene variations had added value to conventional risk factors in predicting chronic periodontitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study validated the influence of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101 genetic factors on the severity of chronic periodontitis in four different ethnicities.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12181","type":"journal-article","created":{"date-parts":[[2014,4,2]],"date-time":"2014-04-02T07:28:47Z","timestamp":1396423727000},"page":"52-61","source":"Crossref","is-referenced-by-count":44,"title":["Association of <scp>interleukin<\/scp>\u20101 gene variations with moderate to severe chronic periodontitis in multiple ethnicities"],"prefix":"10.1111","volume":"50","author":[{"given":"X.","family":"Wu","sequence":"first","affiliation":[{"name":"Interleukin Genetics Inc. Waltham MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Offenbacher","sequence":"additional","affiliation":[{"name":"Department of Periodontology University of North Carolina at Chapel Hill Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. J.","family":"L\u03ccpez","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Periodontology Shanghai Stomatological Disease Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.\u2010Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"Interleukin Genetics Inc. 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