Interleukin‐1 Gene Polymorphisms and Chronic Periodontitis in Adult Whites: A Systematic Review and Meta‐Analysis

Abstract

Interleukin-1 (IL-1) gene polymorphisms have been associated with increased levels of inflammatory mediators and several inflammatory diseases. Periodontitis is a bacterially induced chronic inflammatory disease that destroys the connective tissues and bone that support the teeth, affects substantial numbers of adults, and has been implicated as a contributing factor in systemic diseases. IL-1 gene polymorphisms, most prominently IL1A (-889), IL1A (+4845), and IL1B (+3954), have been associated with chronic periodontitis (CP) in whites. Since the first report, ≥125 studies have examined IL-1 gene variation in relation to periodontal disease. These studies have produced mixed findings in diverse periodontal phenotypes and in different ethnic groups. One previous meta-analysis has been published on this topic and supported an association between IL-1 genes and periodontitis, but considerable doubt remains about the patient populations in which the association may be of clinical relevance. A systematic review and meta-analysis was conducted in an attempt to clarify whether IL-1 gene variants were associated with well-defined clinical phenotypes of CP in white patients. Study inclusion criteria focused on the analytic framework originally proposed for the IL-1 genetic effect in which overexpression of inflammatory mediators is hypothesized to result in more severe periodontitis in response to a bacterial challenge. Twenty-seven studies were included in the qualitative analysis. Nineteen studies yielded significant associations between carriage of the minor IL-1 alleles and periodontitis. The meta-analysis, based on 13 qualifying studies, found significant effects for the two individual gene variations (IL1A odds ratio [OR] = 1.48; IL1B OR = 1.54) and for a composite genotype that combines minor alleles at each locus (OR = 1.51). Statistically significant heterogeneity was found that could not be explained, but there was no indication of publication bias. This review and meta-analysis show that IL1A and IL1B genetic variations are significant contributors to CP in whites.