Introduction
Dental fluorosis (DF) is a developmental defect of tooth enamel and can result in various clinical manifestations, ranging from subtle white marks to more severe pitting and discoloration of the teeth [
1,
2]. It’s severity depends on the concentration, duration, and time of exposure to fluoride. The DF is essentially.
Around the world, it was estimated that DF affects particularly Africa, the Eastern Mediterranean and South Asia [
3,
4]. In Tunisia, DF is prevalent, particularly in the northern regions [
3]. To ensure adequate measurement [
4], researchers on DF have shifted to explore it’s underlying genetic origin [
5‐
7]. Single nucleotide polymorphisms (SNPs) [
8] is a useful genetic markers to identify genes associated with complex diseases.
The genetic association with DF was widely studied by previous studies [
9‐
11,
5] The systematic review of Gonzalez et al. [
5] pointed that a total 15 genes and 18 SNPs were associated were associated to DF. Some SNPs were considered risk factors, while others were considered protective factors [
5].
The collagene protein is the most abundant protein in the human body and belongs to family of proteins that strengthen and support many tissues including cartilage, bone, tendon, skin, and the white part of the eye. It has a fundamental role in the bone and soft-tissue formation and presents 78.06% of periodontal ligament fibers, 73.09% of cementum, and 30.50% of alveolar bone [
7]. Given the significant role of the collagen type 1 alpha 2 gene (COL1A2) in bone formation, it is plausible that genetic variants in this gene could influence tooth development, particularly in populations exposed to high levels of fluoride. Detecting these genetic variants may serve as a novel biomarker for DF, helping identify individuals at risk This gene induce the pro-alpha2 (I) chain production which is involved in the fabrication of collagen type I, the most abundant form of collagen in the human body [
7]. It is about 38 kb and is located at 7q21.3– q22.1 region [
12]. Variations in this gene were associated to a numerous pathologies of cartilage, bone and blood vessels. Controversial results were reported about COL1A2 gene and DF [
6,
13,
14]. This information could prove invaluable in identifying an individual’s susceptibility and, in turn, modifying their risk of developing DF.
In this terms, no previous study has been performed among the north African population. Thus, the aim of present investigation was to assess the association between the DF and the rs412777 of COL1A2 gene among a Tunisian population.
Discussion
To date, the DF is widespread in Tunisia, especially in South regions. This alteration would affect various hard tissue like the hypomineralization of enamel, dentin hypercementosis, root resorption and hypermineralization of the cementum [
16]. For the most severe degrees of DF, it can affect the functionality of the tooth because of the important loss of its structure. It would, also, spoil the esthetic appearance of the individuals, especially for severe situations leading to self-esteem problems. Thus, patients are, increasingly, requiring its esthetic management. The psychological impact could be very important altering the life quality particularly for teenagers and young persons. This height exposure for DF, is certainly, associated to the environmental factors including the intake water. However, several studies have proved a link between genetic and DF. Many studies have established this genetic association between DF and polymorphism [
5,
6,
13,
14]. Associated genes, were mainly linked to enamel formation or mineralization [
5].
The present investigation pointed the COL 1A2 polymorphism among the Tunisian population. We investigated the COL1A2 polymorphism, specifically rs412777. The differences between genotypes were found to be statistically significant, indicating that AC and CC genotypes were associated with an increased risk of DF. This finding is consistent with a study by Jarquín-Yáñez et al. [
17], which included 230 children and reported that the presence of the C allele also increased the risk of DF (OR = 2.59, IC95%: 1.60–4.20,
p = 0.05). Unlike Escobar-García et al. [
18], Saha et al. [
19] and Pragya et al [
16] Chakraborty et al. [
20], did not found associations with the same SNP [
18].
Many researchers [
7,
16,
17,
21] investigated the SNPs of COL1A2 gene. They confirmed the association between DF and this gene polymorphism. Variable mutations of the concerned gene were explored: Huang et al. were interested to the rs414408 COL 1 A (OR = 4.85, IC95%: 1.22–19.32). As well, Rahila et al. [
7] with OR = 31.4; IC95%: 3.9–48.7 and OR = 4.0, IC95%: 1.6–10.1). The divergent results may be attributed to the observed polymorphic sequence which might be influenced by different genetic and environmental backgrounds in different ethnic groups.
According to Rahila et al. [
7], this genetic polymorphism was associated to the fluorosis severity. Thus, the comparison within grades of severity of DF was significant (
p < 0.00125) [
7]. However, according to Hung H et al [
21], this genetic susceptibility had no influence on the severity of DF This relationship was not explored in this current study.
The sample size, the differences in protocol used or the difference in population characteristics or environmental factors could explain the controversial results.
In the other hand, the COL1A2 mutation was, also, correlated to diverse disorders. In 2003, Willing et al. [
22] correlated it to hypomineralisation [
7,
22] and decreased bone mineral density. SAHA et al. [
19] stated that the effect of COL1A2 polymorphism is related to regulating the bone mineral density. It can be considered, as well, a genetic risk factor related to the of osteoporosis [
23].
Taking in consideration all these studies, the COL1A2 polymorphism could be a predictor of many others disorders. The Detection of such genes can be used as a novel biomarker osteoporosis. It can be used in identifying person’s susceptibility and there by alter an individual’s risk of developing DF.
The interaction with environmental factor has been proved and associated to the DF The synergistic risk pattern could explain the genetic–environmental interaction. As there is an individual variability in response to external stimuli which may influence the sensitivity to the DF.
In this terms, some studies have instigated others parameters in their studies. Saha et al. [
19] have measured the fluoride concentrations in groundwater, urine, and serum samples. They used a fluoride ion-selective electrode to the fluoride concentrations measurement. High fluoride concentrations water were reported in different regions. The difference was statistically not significant between case and control groups [
19]. Pragya et al. [
16] have, also, measured the fluoride concentration in the for both groups. Close concentrations were reported with Saha et al. [
19]. While Escobar-Garcia D et al. [
18] have quantified fluoride concentrations in tap water and urine which were 4.5 ± 0.46 mg/L and 3.1 ± 0.1 mg/L respectively. They compared the reported concentrations between variable genetic genotypes. Non polymorphic individuals (A/A) showed statistically lower water and urine fluoride concentrations severity (
P = 0.005).
The present study is the first approach of the genetic polymorphism of DF in the Tunisian population. Referring to others surveys conducted in the same topic, the sample size seems to be sufficient [
7,
19]. However, comparing to other investigations, it seems to be insufficient [
6,
20,
21]. The limitation of the sample size was due to the restricted collection period for participants. Additionally, many people were apprehensive and declined to participate.
In the present, the fluoride exposure of every selected individual was not be accurately ascertained. It would be better if the participants were selected from different regions in order to quantify the fluoride exposure. Measuring the fluoride concentration in the affected regions would help identify the endemic cause of DF.
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