Association of a Common Genetic Factor, PTGER3, With Outcome of Periodontal Therapy and Preterm Birth

• Autores: Marjorie K. Jeffcoat, Robert L. Jeffcoat, Nipul Tanna
• Localización: Journal of periodontology, ISSN 0022-3492, Nº. 3, 2014, págs. 446-454
• Idioma: inglés
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• Resumen

  • Background: Clinical evidence suggests an association between preterm birth and periodontal disease. This study explores whether specific genetic polymorphisms are associated with success of periodontal therapy in pregnant women with periodontal disease and, further, whether any of these same polymorphisms are also associated with spontaneous preterm birth (sPTB).

    Methods: One hundred sixty high-risk pregnant women (6 to 20 weeks of gestation) with periodontal disease (?3 sites with attachment loss ?4 mm) were studied. All women received scaling and root planing plus oral hygiene instruction. Periodontal examinations were performed before treatment and 20 weeks later. Participants were classified according to two study outcomes: 1) success or failure of periodontal treatment; and 2) presence or absence of sPTB. Maternal DNA samples from mucosal swabs were characterized using a 1536-SNP (single-nucleotide polymorphism) custom polymerase chain reaction chip. A probabilistic model of each dichotomous outcome, derived using a stepwise Bayesian procedure, was compared to respective null hypotheses on the basis of Monte Carlo simulations and significance estimates obtained using three measures (z-test, Welch t-test, and probability convolution). The models were further confirmed by logistic regression analyses.

    Results: The models revealed a significant relation between a specific polymorphism of prostaglandin E receptor 3 (a gene associated with inflammatory response) and both periodontal treatment failure (odds ratio 11.09, P <0.0002) and sPTB (odds ratio 6.89, P <0.0032).

    Conclusions: These results demonstrate that the risk of unsuccessful periodontal treatment is associated with tag SNPs in specific genes that regulate the inflammatory response, one of which is also associated with sPTB.

    A growing body of evidence shows that periodontal disease is associated with pregnancy outcome.1-5 The results of intervention studies testing whether the incidence of spontaneous preterm birth (sPTB) decreases after periodontal therapy have been primarily, but not universally, positive.6-16 A study in pregnant women showed that successful treatment of periodontal disease15 was associated with a decreased incidence of sPTB. This last finding suggests that host factors may be involved in both the incidence of sPTB and the success of periodontal treatment, a hypothesis consistent with the established role of inflammatory processes in both periodontal disease and parturition.17,18 The research presented here focuses on genetic factors that might help to explain the observed clinical findings.

    Extensive studies have been performed with the goal of defining risk factors for sPTB. Known risk factors include a previous sPTB, low body mass index, and smoking.19 Infections of the genital tract, such as bacterial vaginosis, have been shown to be associated with a higher rate of sPTB,19 and intrauterine infections are believed to be etiologic for many sPTBs, especially those at early gestational ages. sPTB occurs in 13% of the population; of these births, 25% occur in the absence of known risk factors.20 It has long been recognized that gingival inflammation increases in 80% to 90% of women in the course of their pregnancy,21 and the preponderance of the evidence indicates that maternal periodontal disease is associated with an increased incidence of preterm births.3 Much recent work has, therefore, focused on the inflammatory component of periodontal disease as a risk indicator for preterm birth. An association between the presence of periodontal disease and the incidence of sPTB does not, of course, imply that treating the periodontal disease will decrease the incidence of prematurity; while studies on this question have yielded mixed results and are difficult to compare rigorously, many do show a decrease in the incidence in sPTB after a course of simple periodontal treatment (e.g., cleaning above and below the gumline, or daily rinsing with non-alcoholic antimicrobial mouthrinses) that reduced the bacterial plaque and gingival inflammation. 6-16. Pregnant women whose periodontal disease was successfully treated had a significantly lower incidence of sPTB than patients whose treatment was unsuccessful.15 The current authors carried out an intervention study in 160 pregnant women, designed to answer three questions: 1) Is clinical evidence of periodontal treatment failure associated with sPTB? 2) Are specific genetic single-nucleotide polymorphisms (SNPs) associated with failure of periodontal treatment in pregnant women? 3) Are any of these same SNPs associated with sPTB? The study design (randomized, masked, balanced, and controlled for known sPTB risk factors such as smoking, age, and prior PTB) and primary outcomes are described elsewhere.15 That research showed that conventional treatment of periodontal disease by means of scaling and root planing (SRP) was associated in this population with a substantial (as great as 5:1, depending on disease severity) reduction of sPTB. The authors also found, in answer to the first question, that the effect was significantly associated with the clinical success of periodontal therapy, and that patients whose periodontal disease persisted after SRP did not experience much, if any, reduction in sPTB.