Caries and Innate Immunity: <b><i>DEFB1</i></b> Gene Polymorphisms and Caries Susceptibility in Genetic Isolates from North-Eastern Italy

Abstract

Background: The DEFB1 gene, encoding for the constitutively expressed human β-defensin 1 (hBD1) antimicrobial peptide is a potential candidate when studying genetic susceptibility to caries. DEFB1 genetic variations have been reported as contributing to hBD1 production impairment, leading to a greater susceptibility to be infected by oral pathogens, also leading to periodontitis. Methods: We analysed 5 DEFB1 polymorphisms, namely 3 functional single-nucleotide polymorphisms (SNPs) at the 5′-untranslated region (UTR), -52G>A (rs1799946), -44C>G (rs1800972), and -20G>A (rs11362), 2 SNPs at the 3′-UTR, c*5G>A (rs1047031) and c*87A>G (rs1800971) SNP located in potential miRNA binding sites, looking for possible correlations with the risk to develop caries in 654 adult subjects from isolated populations of north-eastern Italy. Dental caries prevalence was evaluated with the DMFT (decayed, missing, filled teeth) index, calculated after an accurate oral examination. DEFB1 SNP genotyping was performed with an Illumina 370k high-density SNP array. Results: Two DEFB1 SNPs were significantly associated with the DMFT index: the strongest association emerged from rs11362 SNP (p = 0.008). In particular G/G homozygous individuals showed a higher DMFT index compared to both G/A heterozygous and A/A homozygous individuals; rs1799946 SNP was also significantly associated with DMFT (p = 0.030), and individuals homozygous for the T allele had a higher DMFT value compared to heterozygous C/T and homozygous C/C individuals. Conclusions: Our study replicated, on a larger number of individuals, previous findings showing the association between two 5′-UTR SNPs in the DEFB1 gene and DMFT, suggesting that these polymorphisms could be considered as potential markers for assessing the risk to develop caries.

The innate host response in caries and periodontitis

“…Clinical caries have not been associated, however, with salivary levels of β‐defensins. Yet, a polymorphism in the gene encoding human β‐defensin 1 (DEFB1) may be associated with higher caries experience (Navarra et al., ) (Navarra et al., ). Whereas AMPs show in vitro activity against a broad spectrum of oral microorganisms, data are needed to show activity in vivo.…”

DEFB1 rs11362 Polymorphism and Risk of Chronic Periodontitis: A Meta-Analysis of Unadjusted and Adjusted Data

“…Defensins comprise a large group of different peptides with 3 disulphide bonds; in the oral cavity, the α- and β-defensins exist in the epithelia, involving gingiva (Krisanaprakornkit et al, 1998; Dale et al, 2001), sulcular fluid (Ganz et al, 1985), saliva, and salivary glands (Zhao et al, 1996; Bonass et al, 1999). They are at high concentrations in healthy and inflamed tissues of the whole body, possibly constituting the first line of defense against pathogens in the mouth (Navarra et al, 2016). Sinceoral cavity has been recognized as a potential reservoir for respiratory pathogens (Mojon, 2002), dental plaque may play an important role in this accident, contributing to periodontal disease (Coulthwaite and Verran, 2007).…”

Evaluation of DEFB1 polymorphisms in individuals with chronic periodontitis and diabetes mellitus type 2 in a population of northeastern Brazil

“…The ‐20A (rs11362) and ‐52 A (rs179946) alleles have been associated, respectively, with the increased (high DMFT—Decayed, Missing teeth due to caries, Filled Teeth; and DMFT—Decayed, Missing teeth due to caries, Filled Surface of a tooth) and decreased (low DMFT) risk of caries in US population . Similarly, the same DEFB1 SNPs (‐20G/G and ‐52T/T genotypes) were associated with DMFT index in an Italian population, also suggesting a potential risk to develop caries . In the context of periodontal disease, the ‐44G/C DEFB1 SNP (rs1800972) was associated with a risk to develop periodontitis in individuals of Ural region (Caucasian) .…”

“…35 Similarly, the same DEFB1 SNPs (-20G/G and -52T/T genotypes) were associated with DMFT index in an Italian population, also suggesting a potential risk to develop caries. 36 In the context of periodontal disease, the -44G/C DEFB1 SNP (rs1800972) was associated with a risk to develop periodontitis in individuals of Ural region (Caucasian). 37 In Japanese individuals, the -44C/C genotype has been associated with susceptibility to periodontitis, particularly with severe CP and with combined severe and moderate CP.…”

“…DEFB1 5′UTR polymorphisms have been related to protein levels alteration and associated with some oral diseases, such as caries and periodontitis . The ‐20A (rs11362) and ‐52 A (rs179946) alleles have been associated, respectively, with the increased (high DMFT—Decayed, Missing teeth due to caries, Filled Teeth; and DMFT—Decayed, Missing teeth due to caries, Filled Surface of a tooth) and decreased (low DMFT) risk of caries in US population .…”