Fine mapping of locus Xq25.1-27-2 for a low caries experience phenotype

Abstract

Objective The purpose of this study was to fine map the locus Xq25.1-27-2 in order to identify genetic contributors involved in low caries experience. Design Seventy-two families from the Philippines were studied. Caries experience was recorded and genomic DNA extracted from peripheral blood was obtained from all subjects. One hundred and twenty-eight polymorphisms in the locus Xq25.1-27-2, a region that contains 24 genes, were genotyped. Association between caries experience and alleles was tested using the transmission disequilibrium test (TDT). This initial analysis was followed by experiments with DNA samples from 1,481 subjects from Pittsburgh, 918 children from Brazil, and 275 children from Turkey in order to follow up the results found in the Filipino families. Chi-square or Fisher’s exact tests were used. Sequencing of the coding regions and exon-intron boundaries of MST4 and FGF13 were also performed on 91 women from Pittsburgh. Results Statistically significant association with low caries experience was found for 11 markers in Xq25.1-27-2 in the Filipino families. One marker was in MST4, another marker was in FGF13, and the remaining markers were in intergenic regions. Haplotype analysis also confirmed these results, but the follow up studies with DNA samples from Pittsburgh, Brazil, and Turkey showed associations for a subset of the 11 markers. No coding mutations were identified by sequencing. Conclusions Our study failed to conclusively demonstrate that genetic factors in Xq25.1-27-2 contribute to caries experience in multiple populations.

Single Nucleotide Polymorphism in the Aetiology of Caries: Systematic Literature Review

“…Studies of genetic mechanisms in the aetiology of caries encompass, primarily, 4 main groups of genes responsible for (1) development of the enamel, (2) formation and composition of saliva, (3) immunological response, and (4) carbohydrate metabolism [Shuler, 2001;Darshana et al, 2014]. Genome-wide scan studies conducted by Vieira et al [2008] revealed the association of loci 5q13.3, 14q11.2, and Xq27.1 with low caries vulnerability, which was confirmed later by Shimizu et al [2013] and Küchler et al [2014]. On the other hand, loci 13q31.1 and 14q24.3 were connected with high caries susceptibility .…”

Fine-Mapping of Xq25.1–27.2 Shows Association of Early Childhood Caries with Genetic Variants Depending on Dietary Habits, Protecting Children Who Drink Milk before Going to Bed

“…1) are flanking FGF13. Originally [Vieira et al, 2008], we found linkage with Xq25.1-27.2, and the fine-mapping of the locus [Küchler et al, 2014] suggested association with FGF13, but after sequencing the coding regions of the gene, we did not find any causative mutations. Interestingly, the results of the present study showed association with markers flanking FGF13.…”

“…After the initial mapping of chromosome X as potentially involved in caries experience [Vieira et al, 2008] and an inconclusive set of results attempting to fine-map the locus [Küchler et al, 2014] role of chromosome X in dental caries may be more evident under specific dietary conditions. According to the UCSC Genome Browser, the locus that we studied has 88 genes, and the statistically associated markers (Fig.…”

“…A nonparametric logarithm of the odds score p value of 0.0005 was found when the analysis considered low caries experience rates the phenotype. We explored these initial results in data and samples from more than 3,000 individuals [Küchler et al, 2014], and it was difficult to interpret the findings. We hypothesized that the nonconclusive results are due, at least in part, to the inability to include relevant information such as dietary habits and oral hygiene as covariates in the analysis.…”

Effects of chlorhexidine varnish on caries during orthodontic treatment: a systematic review and meta-analysis

“…Caries is a clinical and etiological heterogeneous condition 1 and is a major oral health problem in most industrialized countries. 2 Caries can present as a cavitated lesion, or as a non-cavitated lesion, also referred to as a white spot lesion (WSL).…”