Polymorphisms in genes expressed during amelogenesis and their association with dental caries: a case–control study

Abstract

Objectives Dental caries is a widespread multifactorial disease, caused by the demineralization of hard dental tissues. Susceptibility to dental caries is partially genetically conditioned; this study was aimed at finding an association of selected single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in amelogenesis with this disease in children. Materials and methods In this case–control study, 15 SNPs in ALOX15, AMBN, AMELX, KLK4, TFIP11, and TUFT1 genes were analyzed in 150 children with primary dentition and 611 children with permanent teeth with/without dental caries from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) cohort. Results Dental caries in primary dentition was associated with SNPs in AMELX (rs17878486) and KLK4 (rs198968, rs2242670), and dental caries in permanent dentition with SNPs in AMELX (rs17878486) and KLK4 (rs2235091, rs2242670, rs2978642), (p ≤ 0.05). No significant differences between cases and controls were observed in the allele or genotype frequencies of any of the selected SNPs in ALOX15, AMBN, TFIP11, and TUFT1 genes (p > 0.05). Some KLK4 haplotypes were associated with dental caries in permanent dentition (p ≤ 0.05). Conclusions Based on this study, we found that although the SNPs in AMELX and KLK4 are localized in intronic regions and their functional significance has not yet been determined, they are associated with susceptibility to dental caries in children. Clinical relevance AMELX and KLK4 variants could be considered in the risk assessment of dental caries, especially in permanent dentition, in the European Caucasian population.

Association of KLK4 rs2235091 polymorphism with susceptibility to dental caries: a systematic review and meta-analysis

“…Four articles were entered into our meta-analysis ( 13 – 16 ) ( Figure 1 ), involving 848 individuals with caries and 463 controls. Among the four articles included, one article contained two studies ( 16 ).…”

“…Four articles were entered into our meta-analysis ( 13 – 16 ) ( Figure 1 ), involving 848 individuals with caries and 463 controls. Among the four articles included, one article contained two studies ( 16 ). Besides, one article did not report the number per genotype in the cases and control group, but reported the corresponding OR values in both homozygous (GG vs. AA: OR = 1.58, 95% CI: 0.38–6.55) and heterozygous (GA vs. AA: OR = 1.58, 95% CI: 0.38–6.55) models ( 13 ).…”

“…Sensitivity analysis was performed on the results of primary dentition. The pooled results showed that, except in the recessive and heterozygous models, differences changed significantly after the removal of one article ( 13 ), one article ( 15 ), and one article ( 16 ) in the allelic, dominant, and homozygous genetic models, respectively ( Figures 3A–E ). This suggested that the findings obtained in the primary dentition had instability in this meta-analysis.…”

“…Zaorska et al ( 15 ) showed that allele G of KLK4 rs2235091 could increase the risk of DC in primary dentition. However, Gachova et al ( 16 ) reported that the allele G at KLK4 rs2235091 locus was not associated with the DC risk in primary dentition compared with the A allele. Therefore, in this study, we used a method of systematic review and meta-analysis to explore this association and provide an evidence-based medical basis for the etiological exploration of DC.…”

“…There are several existing publications reporting the relationship of susceptibility to DC with KLK4 rs2235091 gene polymorphism ( 13 – 16 ), but the conclusions are still controversial. Zaorska et al ( 15 ) showed that allele G of KLK4 rs2235091 could increase the risk of DC in primary dentition.…”