title: Association of interleukin-1 gene variations with moderate to severe chronic periodontitis in multiple ethnicities.
abstract: OBJECTIVE
  Genetic markers associated with disease are often non-functional and generally tag one or more functional "causative" 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-1 (IL-1) gene variations across multiple ethnic populations to replace the non-functional markers originally associated with chronic adult periodontitis in Caucasians.
  
  
  METHODS
  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 IL1B gene single nucleotide polymorphisms (SNPs), including three functional SNPs (rs16944, rs1143623, rs4848306) in the promoter and one intronic SNP (rs1143633), were determined using a single base extension method or TaqMan 5' nuclease assay. Logistic regression and other statistical analyses were used to examine the association between moderate to severe periodontitis and IL1B gene variations, including SNPs, haplotypes and composite genotypes. Genotype patterns associated with disease in the discovery study were then evaluated in independent validation studies.
  
  
  RESULTS
  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 IL1B gene, including a pattern of four IL1B SNPs (OR = 1.87, p < 0.0001). The association between the disease and this IL1B composite genotype pattern was validated in two additional studies consisting of Hispanics (OR = 1.95, p = 0.04) or Asians (OR = 3.27, p = 0.01). A meta-analysis of the three populations supported the association between the IL-1 genotype pattern and moderate to severe periodontitis (OR 1.95; p < 0.001). Our analysis also demonstrated that IL1B gene variations had added value to conventional risk factors in predicting chronic periodontitis.
  
  
  CONCLUSIONS
  This study validated the influence of IL-1 genetic factors on the severity of chronic periodontitis in four different ethnicities.
authors.affiliation: Interleukin Genetics Inc., Waltham, MA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: S
authors.initials: S
authors.lastname: Offenbacher
authors.forename: N J
authors.initials: NJ
authors.lastname: Lόpez
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: H-Y
authors.initials: HY
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Rogus
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: J
authors.initials: J
authors.lastname: Beck
authors.forename: S
authors.initials: S
authors.lastname: Jiang
authors.forename: X
authors.initials: X
authors.lastname: Bao
authors.forename: L
authors.initials: L
authors.lastname: Wilkins
authors.forename: L
authors.initials: L
authors.lastname: Doucette-Stamm
authors.forename: K
authors.initials: K
authors.lastname: Kornman
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002677:Chile / Q000208:ethnology; D002681:China / Q000208:ethnology; D055113:Chronic Periodontitis / Q000235:genetics / Q000276:immunology*; D015331:Cohort Studies; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007199:Indians, South American / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D014481:United States / Q000208:ethnology; D044465:White People / Q000235:genetics
chemical_list: D053583:Interleukin-1beta
keywords: genetic risk; interleukin-1; multiple ethnicities; periodontitis