Assessment of the Clinical Validity and Utility of SNPs When Used as Predictors for Periodontitis
thesisposted on 2017-10-27, 00:00 authored by Julio E Obando
BACKGROUND Chronic periodontitis is an inflammatory disease, influenced by a multifactorial etiology; susceptible host, environmental factors, microbial colonization and genetic variations. As genes determine qualitative and quantitative aspects of immunological responses, efforts are being directed to identification of genetic polymorphisms that can be used to predict disease susceptibility. Several single nucleotide polymorphisms (SNPs); IL-1 alpha (-889) rs1800587, IL-1 alpha (+4845) rs17561, IL-1 beta (+3935) rs1143634, IL-1RN (+2018) rs419598 and IL-6 (-174) rs1800795 have been associated with periodontitis. These SNPs have been incorporated into genetic tests to assess the risk of chronic periodontitis. Purpose To assess the clinical validity and utility of 5 interleukin SNPs as genetic tests for periodontitis. MATERIALS AND METHODS A scoping review through PubMed and EMBASE was queried to identify reports of 5 SNPs (rs1800587, rs17561, rs1143634, rs419598 and rs1800795) for individuals with periodontitis or healthy periodontium. Data from 1000 Genomes Project (http://browser.1000genomes.org/) were used to estimate the percentage of individuals expected to carry each genotype for African Americans, Han Chinese, Northern Europeans and Caucasian North Americans. Two models depending on the risk factor genotype were performed for each SNP: Model 1 homozygous genotype = disease. Model 2 homozygous and heterozygous genotype = disease. Allele frequency distributions were calculated using Hardy Weinberg equilibrium. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS The different SNPs assign a very different proportion of high risk individuals in each population. rs1143634 is used in the Asian population 2% of the allele A (or T) is present in contrast with rs419598, which have a frequency of 91% of the allele T. The minor allele frequency (MAF) of IL-1B for the Southern Han Chinese is 2% compare to a 74% when using IL-6 as a genetic tool. For the Africa American population the MAF ranges from 16% to 51%, depending on which SNP is using as a risk assessment. Ranges of sensitivity (13%-32%), specificity (69%-88%), PPV (52%-56%) and NPV (48%-61%) from literature scoping were calculated for rs17561, rs1143634, rs1800975 and found a low efficacy and efficiency for each SNP. CONCLUSION The clinical validity and clinical utility of these SNPS to predict risk for periodontitis is not supported by these data.