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Polymorphic regions in the interleukin-1 gene and susceptibility to chronic periodontitis: a genetic association study.

ABSTRACT: The objectives of this study were to determine the association between single nucleotide polymorphisms (SNPs) in IL1B (-511, +3954), IL1A (-889, +4845), and the variable number of tandem repeats (VNTRs) polymorphism in the IL-1RN gene with chronic periodontitis susceptibility and to analyze gene-gene interactions in a hospital-based sample population from South India.A total of 400 individuals were recruited for this study; 200 individuals with healthy gingiva and 200 chronic periodontitis patients. Genomic DNA was isolated from peripheral blood samples and genotyping was performed for the above-mentioned single nucleotide and VNTR polymorphisms by polymerase chain reaction, DNA sequencing, and agarose gel electrophoresis.A higher proportion of the variant alleles were observed in the chronic periodontitis group for all the SNPs examined. The SNP at +3954 (C>T) in the IL1B gene was found to be significantly associated with chronic periodontitis (p=0.007). VNTR genotypes (?(2) value: 5.163, df=1, p=0.023) and alleles (?(2) value: 6.818, df=1, p=0.009) were found to have a significant association with chronic periodontitis susceptibility.In the study population examined, the SNP in the IL1B gene (+3954) and VNTR polymorphisms in the IL1RN gene were found to have a significant association with chronic periodontitis susceptibility.

SUBMITTER: Lavu V

PROVIDER: S-EPMC4394157 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Polymorphic regions in the interleukin-1 gene and susceptibility to chronic periodontitis: a genetic association study.

Lavu Vamsi V Venkatesan Vettriselvi V Venkata Kameswara Subrahmanya Lakkakula Bhaskar B Venugopal Priyanka P Paul Solomon Franklin Durairaj SF Rao Suresh Ranga SR

Genetic testing and molecular biomarkers 20150224 4

<h4>Objective</h4>The objectives of this study were to determine the association between single nucleotide polymorphisms (SNPs) in IL1B (-511, +3954), IL1A (-889, +4845), and the variable number of tandem repeats (VNTRs) polymorphism in the IL-1RN gene with chronic periodontitis susceptibility and to analyze gene-gene interactions in a hospital-based sample population from South India.<h4>Subjects and methods</h4>A total of 400 individuals were recruited for this study; 200 individuals with heal ...[more]

PMID: 25710474

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Project description:Background and objectiveGenetic 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.Material and methodsAdult 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.ResultsSignificant 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.ConclusionThis study validated the influence of IL-1 genetic factors on the severity of chronic periodontitis in four different ethnicities.

Dataset Information

Polymorphic regions in the interleukin-1 gene and susceptibility to chronic periodontitis: a genetic association study.

Publications

Polymorphic regions in the interleukin-1 gene and susceptibility to chronic periodontitis: a genetic association study.

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