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 Table of Contents  
Year : 2023  |  Volume : 15  |  Issue : 5  |  Page : 449-453

Do Polymorphisms predispose dental caries susceptibility in Egyptian adults? A cross-sectional study

Department of Conservative Operative Dentistry, Faculty of Dentistry, October 6 University, Giza, Egypt

Date of Submission12-May-2023
Date of Decision11-Sep-2023
Date of Acceptance18-Sep-2023
Date of Web Publication30-Oct-2023

Correspondence Address:
Hassan M H Negm
Department of Conservative Operative Dentistry, Faculty of Dentistry, October 6 University, Giza 12585
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jioh.jioh_112_23

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Aim: Understanding how specific genetic variations related to dental caries in understudied populations can pave the way for more personalized approaches to oral health care. The study is designed to explore the correlation between three genetic polymorphisms in Egyptian adults. Materials and Methods: We included 132 young adults aged 15–22 years, with an equal distribution of males and females, randomly selected from secondary Cairene school. The participants were in good health, without hereditary diseases, and had no recent dental treatment. Dental exams were conducted using standardized criteria, with reliability ensured between examiners. DNA collection was performed using buccal swabs, and DNA purification was carried out according to the manufacturer’s instructions. Samples were stored at −21°C for future analysis. We selected specific single nucleotide polymorphisms (SNPs) for ENAM rs3796703, DEFB1 rs11362, and AMELX rs946252 for genotyping. χ2 test and its corresponding statistical significance were calculated. Results: Specific genetic variations, particularly ENAM rs3796703, AMELX rs946252, DEFB1 rs11362, and KLK4 rs2242670, were found to be significantly linked to an elevated caries risk in the group predisposed to caries. These particular genetic variations were notably more prevalent among individuals at a higher risk of developing dental caries. Conclusion: The DEFB1 rs11362 AG genotype showed significance, notably associated with a high DMFT index, particularly in individuals with severe and proximal caries. In contrast, the ENAM rs3796703 polymorphism revealed similar frequencies of allele C and allele T in both caries-susceptible and caries-resistant groups, with genotype CT being significantly associated with reduced dental caries susceptibility. KLK4 rs2242670 did not reveal significant associations with dental caries susceptibility, indicating that this gene polymorphism.

Keywords: Beta-Defensin 1, Enamelin, KLK4, Polymorphisms

How to cite this article:
Negm HM. Do Polymorphisms predispose dental caries susceptibility in Egyptian adults? A cross-sectional study. J Int Oral Health 2023;15:449-53

How to cite this URL:
Negm HM. Do Polymorphisms predispose dental caries susceptibility in Egyptian adults? A cross-sectional study. J Int Oral Health [serial online] 2023 [cited 2023 Dec 2];15:449-53. Available from:

  Introduction Top

Conducting genetic research on dental caries in understudied populations is significant because it can lead to a deeper understanding of the disease, personalized healthcare approaches, improved public health strategies, and more equitable healthcare outcomes. There have been suggestions of a connection between mutations in the ENAM, DEFB1, KLK4, and AMELX genes and susceptibility to dental caries.[1] The KLK4 gene encodes for kallikrein-related peptidase 4, an enzyme that is involved in the breakdown of proteins. Variations in this gene, represented by different single nucleotide polymorphisms (SNPs), have been studied in relation to dental caries susceptibility. Dental caries is a complex condition that results from a combination of genetic, environmental, and lifestyle factors, illustrating its multifactorial nature.[2] The associations of certain KLK4 genotypes (like rs198968 and rs198969) with dental caries susceptibility were investigated. However, the conclusion of whether these genotypes are considered cariogenic or not depends on the results of the statistical analyses across ethnicities.[3] DEFB genes are located on chromosome 8p23.1 and exhibit significant copy number variations, except for DEFB1, making it suitable for straightforward genetic susceptibility analysis. Within the DEFB1 gene, various SNPs have been identified, including the rs11362 polymorphism, which is located in the promoter region and influences a key nuclear factor kappa B (NF-kB) transcription-binding site.[4],[5],[6]

Genetic variations within the ENAM gene, exemplified by rs3796704, rs12640848, and rs7671281, have been linked to dental caries susceptibility (DCS). These genetic variances can induce modifications in the structure or functionality of the ENAM protein, potentially influencing enamel mineralization and its organizational structure.[7],[8]

AMELX plays a pivotal role in regulating the production of amelogenin, a fundamental protein in enamel development. Genetic polymorphisms within AMELX can result in discernible alterations in enamel microstructure. These changes in the microstructure of enamel can significantly impact its strength and resilience against dental caries.[9],[10] Potential connections between genetic components and dental caries were explored, with a specific focus on the roles of KLK4 and DEFB1.[11]

This study seeks to address these gaps by investigating the distributional differences of polymorphic loci, specifically ENAM rs3796703, DEFB1 rs11362, and KLK4 rs2242670, in Egyptian adults. This research aims to identify genetic factors that may contribute to the heightened DCS observed in pediatric populations. Our study is motivated by the necessity to unravel the genetic underpinnings of DCS. Our goal in comprehending these genetic factors is to gain insights into the heightened susceptibility of specific individuals in this population to dental caries, especially when environmental factors alone cannot fully account for this phenomenon.

  Materials and Methods Top

Dental examination

Following the securing of the institutional ethical approval, this study included 132 young adults aged 15–22 years, of males (72) and females), (60) selected from secondary schools in major cities of Greater Cairo. Participants were randomly chosen from school lists, with an average age of 17 years. They had to be in good health, without hereditary diseases, and not have received recent dental treatment. Dental exams used standardized criteria, and reliability was ensured between examiners. A control group was included for comparison as previously described.[12]

The careful assessment of inter-examiner reliability is of paramount importance. It serves as a shield against potential examiner bias and fortifies the study’s validity to ensure that the findings are grounded in objectivity and accuracy. The inclusion of a matched control group is more than a procedural step to enable meaningful comparisons and pinpoint the effects of the variables under scrutiny. This approach ensures that any observed differences are attributable to the specific factors we are investigating, rather than being confounded by unrelated variables. The presentation of comprehensive data on caries prevalence across various demographics, including age groups, urban and rural communities, and distinct ethnicities, offers invaluable insights. It lays bare the patterns and disparities in dental caries distribution among different population segments. By targeting specific demographics, we can enhance oral health outcomes more effectively.

For improving external validity, the target population—adults from primary schools in major cities of Greater Cairo—were made representative of diverse capital city-level or ethnic groups. This ensures that the findings are not isolated but rather applicable to broader populations and specific ethnic groups.

Prior to commencing the oral examination, air scavenging was applied, ensuring a clear field for recording the carious status. A total of 148 adult patients were enrolled in this study, with an equivalent number of patients serving as controls. Within the caries-susceptible group, white-spot lesions were also documented but were not included in the subsequent analysis. Sample size determination was based on achieving a statistical power of 80%, guided by insights gained from a pilot study.

DNA collation

In this study, DNA was collected from all participants using buccal swabs provided in the Sigma Cheek Cell Collection Kit. These swabs were gently rubbed on both sides of the buccal mucosa ten times. The collected swabs were placed in 1.5-mL Eppendorf tubes after removing the plastic sticks from the swabs. These tubes were then stored at +4°C until genomic DNA extraction. Following a brief centrifugation, DNA purification was performed in accordance with the manufacturer’s instructions. The purified DNA samples were subsequently stored at −21°C for future analysis.

Distinct identification codes were allocated to the samples, ensuring privacy by refraining from employing personal identifiers such as names. Those responsible for the sample analysis and interpretation remained uninformed about the subjects’ personal information and clinical traits. These identification codes were utilized to mark the samples and all connected data. Using codes instead of personal details helps safeguard the privacy and confidentiality of the study participants. This is particularly important in research to ensure that individuals cannot be identified or linked to their specific data, which helps maintain their privacy rights. As knowledge of personal information could inadvertently influence the researchers’ judgments or interpretations, data were coded.

Single nucleotide polymorphism selection and genotyping

We used the following SNPs for the following genes.

ENAM rs3796703 (forward primer: 5′-AGAGGACCC​AGTTGATCCAA-3′, reverse primer: 3′-AAATGTG​TTGCCTGATCCCA-5′), DEFB1 rs11362 (forward primer: 5’-CAGCTCAG​CCTCCAAACG-3’, reverse primer 5′-GCAGGTACCA​GAGCTTACC-3), AMELX rs946252 (forward primer: 5′- TGTTTTAA​ACCCTAATTTCACCAACTAGGA-3′, reverse primer: 3′-CCAGGGATTTGGAAAGTTGGG-5′).

We conducted polymerase chain reaction (PCR) using a Mastercycler Gradient thermal cycler from Eppendorf, located in Hamburg, Germany. Subsequently, the generated products were subjected to sequencing utilizing an ABI 3730XL Automatic Sequencer, which is based in CA, USA. To assess the Hardy–Weinberg equilibrium within the study groups, we employed the Chi-square test. Our predefined threshold for statistical significance was set at P < 0.05.

The study adhered to the STROBE guidelines throughout its design, data collection, analysis, and reporting. These guidelines are designed to enhance the quality and transparency of observational studies, ensuring the reliability and validity of the research findings.

  Results Top

Polymorphisms represent genetic variations within a population. These variations can affect the structure or function of certain genes related to dental health. Some polymorphisms may lead to differences in the production or function of proteins involved in tooth enamel formation, saliva composition, or immune response, all of which are factors that can influence susceptibility to dental caries. This study examined the impact of genetics and the environment on dental caries in Egyptian adults through the genotyping of three specific SNPs. The AG genotype of DEFB1 rs11362 displayed significance and was linked to a high DMFT index, especially in individuals with severe and proximal caries. One of the gene polymorphisms investigated in this study was ENAM rs3796703. Interestingly, we observed that both caries-susceptible and caries-resistant groups had similar frequencies of allele C and allele T, with no significant differences between the two groups. However, when examining specific genotypes, we found that genotype CT exhibited a statistically significant association with dental caries susceptibility (χ2 = 2.33, P = 0.003). The odds ratio for this association was 0.44 (0.37–0.66), suggesting that individuals with genotype CT may be less susceptible to dental caries.

Polymorphisms in genes related to the immune system, such as DEFB1, can influence an individual’s ability to combat oral bacteria and prevent dental caries. Variations in these genes may impact the production of antimicrobial peptides and affect the body’s defense mechanisms against oral pathogens. Our analysis of DEFB1 rs11362 did not reveal any significant associations with dental caries susceptibility. Allele G and allele A were equally distributed in both the caries-susceptible and caries-resistant groups, indicating that this specific gene polymorphism may not play a substantial role in the susceptibility to dental caries in this population.

Another gene polymorphism we investigated was AMELX rs946252. Similar to ENAM rs3796703, we observed that allele C and allele T had comparable frequencies in both groups. However, genotype CT exhibited a statistically significant association with dental caries susceptibility (χ2 = 3.11, P = 0.013), with an odds ratio of 0.036 (0.23–0.95). This suggests that individuals with genotype CT may have a reduced susceptibility to dental caries.

Finally, the genetic analysis of KLK4 rs2242670 did not reveal any significant associations with dental caries susceptibility. Allele A/G and allele A/T were evenly distributed in both the caries-susceptible and caries-resistant groups, indicating that this gene polymorphism may not be a strong contributor to dental caries susceptibility in this population.

Overall, we found significant associations between ENAM rs3796703 and AMELX rs946252 gene polymorphisms with dental caries susceptibility, while DEFB1 rs11362 and KLK4 rs2242670 showed no significant associations [Table 1]. These findings suggest that specific genetic variations may influence an individual’s predisposition to dental caries.
Table 1: χ2 measures for the studied SNPs in Egyptian children

Click here to view

  Discussion Top

Identifying specific genetic variations associated with increased susceptibility allows for personalized risk assessment. This knowledge can help individuals and healthcare providers tailor preventive strategies and interventions to those at higher risk. Genome-wide association studies (GWAS) have been instrumental in pinpointing genetic variations linked to caries susceptibility. These investigations have deepened our understanding of the genetic components influencing caries.[13] Caries experience was determined primarily using DMFT scores (decayed, missing, filled teeth), with adjustments for subject age to address DMFT score limitations. Further research is warranted, including the prioritization of specific genetic regions, refining of phenotype definitions, and exploration of how genetic variants within gene sets interact.[3]

Much as ENAM rs3796703 and AMELX rs946252 gene polymorphisms were found deterministic in several populations,[8] results were conflicting regarding the cariogencity of KLK4[14],[15],[16] and DEFB1.[5],[17],[18]

A crucial role of the DEFB1 gene, particularly variants rs11362 and rs1799946, in dental caries susceptibility among Chinese children was suggested. The results of the association analysis revealed a strong link between the DEFB1 gene variant rs11362 and dental caries susceptibility. Children carrying this variant were significantly more susceptible to dental caries, with an odds ratio (OR) of 2.447, indicating a higher risk of developing dental caries. Moreover, rs11362 showed a positive correlation with the severity of dental caries, suggesting that this gene variant contributes to both susceptibility and severity. Another variant of the DEFB1 gene, rs1799946, also demonstrated a significant association with dental caries susceptibility, particularly in the severe group of affected children. In this group, children carrying rs1799946 had a significantly lower risk of dental caries (OR = 0.473), indicating a protective effect. This protective effect was consistent when analyzing the group comprising both moderate and severe cases (OR = 0.623).[18] However, consistent with our study, Navara et al.[18] found that two DEFB1 SNPs exhibited significant associations with the DMFT index. The strongest association was observed with the rs11362 SNP (P = 0.008). Those who possessed the G/G variant in a homozygous state exhibited a higher DMFT index than individuals who were either G/A heterozygous or A/A homozygous. Moreover, the rs1799946 SNP also exhibited a significant association with DMFT (P = 0.030), wherein individuals homozygous for the T allele displayed a higher DMFT value when compared to those who were heterozygous C/T or homozygous C/C.[19]

The KLK4 gene, located at 19q13.41, has been of interest in studies investigating its potential connection to dental caries susceptibility.[20] Moreover, two variants, KLK4/rs2235091 and KLK4/rs198968, were examined. This cross-sectional study focused on a cohort of children aged 2–5 years in Turkey. The study encompassed a total of 259 participants, further categorized into 123 individuals classified as caries-free and 137 with caries experience. The study investigated the role of these KLK4 variants within the gene’s intron, with one being a genic downstream transcript variant and the other a genic upstream transcript variant. The findings aimed to shed light on the potential influence of these variants on dental caries susceptibility in this specific age group and geographical region.[21]

Another KLK4 variant, KLK4/rs198969, was examined in a case-control study conducted by Gerreth et al.[2] in 2017. This study focused on a population in Poland, comprising children aged 20–42 months. In this research, a total of 96 participants were included, equally divided into cases (those with dental caries) and controls (caries-free individuals). The specific variant studied was located in the genic upstream transcript variant region of KLK4. This investigation aimed to determine whether this KLK4 variant played a role in dental caries susceptibility within this particular Polish population of young children.[10] Considering diverse populations, age groups, and geographical locations, provides valuable insights into the potential genetic factors contributing to dental caries, especially with geriatric patients developing prostate cancer.

  Conclusions Top

Genetic polymorphisms associated with dental caries susceptibility contribute to a deeper understanding of the disease’s underlying mechanisms. This knowledge can aid in the development of novel treatments and preventive approaches targeting specific genetic pathways. We examined genetic anomalies in AMELX, ENAM, and LTF genes. Anomalies in ENAM rs3796703 and AMELX rs946252 were frequently observed in individuals prone to caries, implying a potential link between these protein defects and dental caries severity. DEFB1 rs11362 polymorphisms were associated with elevated DMFT index values (≥7) among Egyptian adults. Further research is required to explore the potential synergistic effects of MUC1, NKX2-3, PROM1, CD14, and CDKN1A in contributing to dental caries susceptibility in Egyptian adults. Studying these genetic variations helps to fathom why some individuals are more prone to dental caries with therapeutic implications in personalized dentistry.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

Authors contributions

Dr. Hassan M. H. Negm is the sole author.

Ethical policy and Institutional Review board Statement

IRB Number: AUAREC202200006-12, obtained on April 16, 2023.

Patient declaration of consent

Not applicable.

Data Availability Statement

Data will be made available upon reasonable request.

  References Top

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