The Role of Polymorphisms at the Interleukin-1, Interleukin-4, GATA-3 and Cyclooxygenase-2 Genes in Non-Surgical Periodontal Therapy

Kay-Arne Walther, José Roberto Gonzales, Sabine Gröger, Benjamin Ehmke, Dogan Kaner, Katrin Lorenz, Peter Eickholz, Thomas Kocher, Ti-Sun Kim, Ulrich Schlagenhauf, Raphael Koch, Jörg Meyle, Kay-Arne Walther, José Roberto Gonzales, Sabine Gröger, Benjamin Ehmke, Dogan Kaner, Katrin Lorenz, Peter Eickholz, Thomas Kocher, Ti-Sun Kim, Ulrich Schlagenhauf, Raphael Koch, Jörg Meyle

Abstract

Periodontitis is a multifactorial disease. The aim of this explorative study was to investigate the role of Interleukin-(IL)-1, IL-4, GATA-3 and Cyclooxygenase-(COX)-2 polymorphisms after non-surgical periodontal therapy with adjunctive systemic antibiotics (amoxicillin/metronidazole) and subsequent maintenance in a Caucasian population. Analyses were performed using blood samples from periodontitis patients of a multi-center trial (ClinicalTrials.gov NCT00707369=ABPARO-study). Polymorphisms were analyzed using quantitative real-time PCR. Clinical attachment levels (CAL), percentage of sites showing further attachment loss (PSAL) ≥1.3 mm, bleeding on probing (BOP) and plaque score were assessed. Exploratory statistical analysis was performed. A total of 209 samples were genotyped. Patients carrying heterozygous genotypes and single-nucleotide-polymorphisms (SNP) on the GATA-3-IVS4 +1468 gene locus showed less CAL loss than patients carrying wild type. Heterozygous genotypes and SNPs on the IL-1A-889, IL-1B +3954, IL-4-34, IL-4-590, GATA-3-IVS4 +1468 and COX-2-1195 gene loci did not influence CAL. In multivariate analysis, CAL was lower in patients carrying GATA-3 heterozygous genotypes and SNPs than those carrying wild-types. For the first time, effects of different genotypes were analyzed in periodontitis progression after periodontal therapy and during supportive treatment using systemic antibiotics demonstrating a slight association of GATA-3 gene locus with CAL. This result suggests that GATA-3 genotypes are a contributory but non-essential risk factor for periodontal disease progression.

Keywords: Cyclooxygenase-2; GATA-3; Interleukin-1; Interleukin-4; antibiotics; periodontal therapy; periodontitis; polymorphisms; risk factor.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Boxplots of GATA-3: Mean CAL differences to visit 2 (a) and to visit 4 (b) in the total collective: * p-values are from Mann–Whitney U-tests for the pairwise comparison with the wild-type group. Negative values represent an improvement and positive values represent a deterioration. Abbreviations: CAL: mean clinical attachment level per patient, SNP: single nucleotide polymorphism, mm: millimeter, × marks the mean.

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