Effect of fluoride in drinking water on the level of 5-methylcytosine in human and rat blood.

DNA methylation is an epigenetic modification of genome that is involved in many human diseases. Recent studies revealed DNA methylation may be associated with fluorosis. This study was aimed to evaluate the dose-response effect of fluoride on DNA methylation in human and rat blood. A commercial ELISA kit was employed to evaluate 5-methylcytosine (5-mC) level of genome in human and rat blood. A total of 281 subjects were enrolled in this study and divided into four equal-size groups by the quartile of fluoride in drinking water. The difference of 5-mC among the four groups was significant. The U-shaped relationship was found between fluoride and 5-mC in the population. The U-shaped curve was also observed in the rats with three months of fluoride treatments. Taken together, these results clue the disruption of DNA methylation in mammals may has a certain association with fluoride in natural exposures.

Gastrodin alleviates bone damage by modulating protein expression and tissue redox state.

Fluorosis is a common disease characterized by disruptions in bone metabolism and enamel development. The production of reactive oxygen species is thought to play an important role in fluorosis. Gastrodin (4-hydroxybenzylalcohol4-O-beta-D-glucopyranoside) has been reported to have antioxidative activity, and so here we examined whether gastrodin has protective effects against oxidative stress and bone tissue toxicity in rats with fluorosis. Wistar rats were given different doses of gastrodin 1 month after fluoride administration, and samples of blood, bone and teeth were collected after 2, 3 and 4 months; glutathione peroxidase glu, CAT and SOD levels in the fluorosis group were lower than those in the control group. Gastrodin treatment in rats ameliorated oxidative stress and fluoride accumulation that were induced by fluoride; treatment with 400 mg·kg-1 gastrodin protected trabecular bone structure and reduced femur and alveolar bone injury in rats with fluorosis. Enhanced expression of cysteinyl aspartate-specific proteinase (caspase) 3, caspase-9 and Bax and decreased expression of Bcl-2 induced by fluoride were also reversed by gastrodin. In summary, the present data suggest that gastrodin, and in particular a dose of 400 mg·kg-1 , can improve the antioxidative capacity of rats, reduce concentration of fluoride in tissues, alleviate bone damage and modulate expression of Bcl-2, Bax, caspase-3 and caspase-9.

Translating from lab-use to household: Dual-functional upconversion nanoprobes for solar-powered photothermal fluorosis diagnosis.

Due to the serious symptoms of brittle bones and endocrine disorders, the common disease fluorosis diminishes quality of life. With the aim of developing probes for both laboratory and household fluorosis diagnosis, in this study we rationally designed a novel dual-functional gallic acid-Fe(III) complex-modified upconversion nanoprobe (DF-UCNP) with simultaneous upconversion luminescence (UCL) and photothermal (PT) conversion capacities. The nanoprobe was feasible for UCL fluorine (F-) detection with a low detection limit of ∼20 nM and a broad linear range of 0-50 µM, as well as UCL fluorosis diagnosis both in vitro and in vivo for lab-use. Furthermore, by utilizing gathered solar irradiation as a PT excitation source and a digital thermometer as a signal reader, the nanoprobe possessed outstanding PT detection capacities for F- with a detection limit of ∼100 nM. Based on this nanoprobe and an accessional self-developed Android application, a household PT kit for fluorosis diagnosis was also constructed. This work provides a new method for rapid laboratory fluorosis diagnosis without a cumbersome determination process as well as household fluorosis diagnosis without requiring specific instruments.

Fluoride Alters Serum Elemental (Calcium, Magnesium, Copper, and Zinc) Homeostasis Along with Erythrocyte Carbonic Anhydrase Activity in Fluorosis Endemic Villages and Restores on Supply of Safe Drinking Water in School-Going Children of Nalgonda District, India.

The present study aimed to determine the serum trace elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg)) along with erythrocyte carbonic anhydrase (CA) activity and effect of intervention with safe drinking water for 5 years in the school children of fluorosis endemic area. For this purpose, three categories of villages were selected based on drinking water fluoride (F): Category I (control, F = 1.68 mg/L), category II (affected F = 3.77 mg/L), and category III (intervention village) where initial drinking water F was 4.51 mg/L, and since the last 5 years, they were drinking water containing < 1.0 mg/L F. The results revealed that urinary F was significantly (P < 0.05) higher in category II compared to categories I and III. A significant (P < 0.05) increase in serum Cu and Mg was observed in category II compared to category I. Serum Zn and Ca was significantly (P < 0.05) decreased in categories II and III compared to category I. The erythrocyte CA activity was decreased in the category II compared to category I. However, in the category III, erythrocyte CA activity was comparable to the control group. In conclusion, F exposure altered elemental homeostasis which has restored to some extent on intervention by safe drinking water for 5 years in school-going children.

Dental fluorosis, nutritional status, kidney damage, and thyroid function along with bone metabolic indicators in school-going children living in fluoride-affected hilly areas of Doda district, Jammu and Kashmir, India.

A case-control study was undertaken among the school children aged 8-15 years to know the presence and severity of dental fluorosis, nutrition and kidney status, and thyroid function along with bone metabolic indicators in Doda district situated at high altitude where drinking water was contaminated and heat stress. This study included 824 participants with an age of 8-15 years. The results of the study reviled that dental fluorosis was significantly higher in affected than control area children. Urinary fluoride was significantly higher (p < 0.05) in affected children as compared to the control area school children. Nutritional status of affected children was lower than control area children. The chronic kidney damage (CKD) was higher in affected than control school children. Thyroid function was affected more in affected than control area schools. Serum creatinine, total alkaline phosphatase, parathyroid hormone, 1, 25(OH)2 vitamin D, and osteocalcin were significantly higher in affected school children (p < 0.05) as compared to control school children, whereas there was no significant difference in triiodothyronine (T3), thyroxine (T4), and 25-OH vitamin D among the two groups. There was a significant decrease in thyroid-stimulating hormone (TSH) in the affected area school children compared to control. In conclusion, fluorotic area school children were more affected with dental fluorosis, kidney damage, along and some bone indicators as compared to control school children.

Gene-environment interaction: Does fluoride influence the reproductive hormones in male farmers modified by ERα gene polymorphisms?

The occurrence of endemic fluorosis is derived from high fluoride levels in drinking water and industrial fumes or dust. Reproductive disruption is also a major harm caused by fluoride exposure besides dental and skeletal lesions. However, few studies focus on the mechanism of fluoride exposure on male reproductive function, especially the possible interaction of fluoride exposure and gene polymorphism on male reproductive hormones. Therefore, we conducted a cross-sectional study in rural areas of Henan province in China to explore the interaction between the estrogen receptor alpha (ERα) gene and fluoride exposure on reproductive hormone levels in male farmers living in the endemic fluorosis villages. The results showed that fluoride exposure significantly increased the serum level of estradiol in the hypothalamic-pituitary-testicular (HPT) axis in male farmers. Moreover, the observations indicated that fluoride exposure and genetic markers had an interaction on serum concentration of follicle-stimulating hormone and estradiol, and the interaction among different loci of the ERα gene could impact the serum testosterone level. Findings in the present work suggest that chronic fluoride exposure in drinking water could modulate the levels of reproductive hormones in males living in endemic fluorosis areas, and the interaction between fluoride exposure and ERα polymorphisms might affect the serum levels of hormones in the HPT axis in male farmers.

High prevalence of dental fluorosis among schoolchildren in three villages in Vavuniya District: an observational study

Background: Studies of groundwater sources in Sri Lanka show that in the entire Northern, North Central, Uva and Eastern Provinces, and also in a large area of the North Western Province, groundwater fluoride content is within the range 1.0 mg/l and 3.0 mg/l. The WHO recommended safe upper limit of fluoride for drinking water is 1.5 mg/l. Objective: Our objective was to determine the prevalence and degree of dental fluorosis in a cohort of schoolchildren in Sinnasippikulam in Vavuniya District, the fluoride content in their serum and urine, and fluoride levels in drinking water in dug wells of the area. Methods: Invitations in Tamil and Sinhala were sent to all households by courier. Demographic information and oral hygiene practices of 307 responsive children were recorded by interviewing children and their mothers. Detailed clinical examinations were performed according to WHO basic methods, with some modifications. Assessment of dental fluorosis in the children was done according to Dean's Index codes and criteria. Results: We found drinking water sources (dug wells) in Sinnasippikulam (n= 82) to have a high mean concentration of fluoride ( x̄ 1.58+ 0.69 mg/l). Of 307 children examined, 224 (72.9%) had clinical evidence of dental fluorosis of varying degrees of severity. The mean fluoride level in serum of schoolchildren was 0.198 mg/l (SD + 0.074; S.E.M. 0.013), and in their urine, 1.44 mg/l (SD + 0.59; SEM 0.11). Conclusions: Our results show that harmful levels of fluoride are extremely common in groundwater sources in the study area, and consequently, dental fluorosis is highly endemic (72.9%) among resident schoolchildren.

[Fluorosis of coal burning affects the male reproductive system].

Fluorosis of coal burning is a new type of endemic fluorosis in China, which affects the male reproductive system. Furthermore, the content of fluoride in the semen, sperm mortality, sperm concentration and the incidence of infertility are higher in severe fluorosis areas than in mild- and non-fluorosis areas, so are the levels of serum follicle-stimulating hormone and luteinizing hormone. However, the levels of inhibin B, serum testosterone and estradiol show different degrees of reduction in severe fluorosis areas. Accordingly, fluorosis of coal burning, just like other endemic fluorosis, may affect the structure of male reproductive organs, the generation of sperm and reproductive endocrinology, resulting in the decline of men's reproductive ability.

The relationship between chemical elements in soil and whole blood, and fluorosis induced by coal-fired pollution.

To study the relationship between chemical elements in soil and whole blood, and fluorosis induced by coal-fired pollution, ecological and case-control studies were carried out. We determined the concentrations of 11 chemical elements and pH values in soil in two fluorosis-affected counties in Chongqing, China, and analyzed the correlation between these values and prevalence of dental fluorosis. Ni, I, F, Hg, and pH values positively correlated with fluorosis prevalence (P < 0.05); these soil parameters may be related to coal-fired pollution fluorosis. Cu, Zn, Ca, Mg, and Fe concentrations in whole blood, and fluoride levels in urine of residents in epidemic and non-epidemic areas were determined. Cu, Zn, Mg, and Fe levels of the children in the case group were lower than those of the children in the external control group; urine fluoride level in the children in the case group was higher than that of the children in the internal and external control groups (P < 0.05). The levels of Mg, Fe, and urine fluoride were higher in the case adult group than in the internal adult control group (P < 0.05). Anti-fluoride elements were deficient in endemic areas.

Increased plasma neopterin and hs-CRP levels in patients with endemic fluorosis.

Although fluoride induced inflammatory reactions have been shown in animals and in vitro humans, there are few studies about fluoride induced inflammatory reactions in human beings at clinical setting. We aimed to measure the plasma neopterin, a marker of activation of the monocyte/macrophage system, and high sensitivity C-reactive protein (hs-CRP) levels in patients with endemic fluorosis to investigate the possible role of inflammatory processes (monocyte/macrophage activity) in the underlying pathophysiology of fluoride toxicity at clinical level. Plasma neopterin and hs-CRP levels were determined in endemic fluorosis patients and control subjects. Plasma neopterin levels were significantly higher among patients with endemic fluorosis when compared with control group (2.40 ± 0.66 vs. 1.63 ± 0.27 ng/mL respectively; p < 0.001) and plasma hs-CRP levels were also significantly higher among patients with endemic fluorosis when compared with control group (2.41 ± 1.23 vs. 1.93 ± 0.64 mg/L respectively; p < 0.001). Plasma neopterin levels were positively correlated with urine fluoride levels (r = 0.67, p < 0.001) and serum hs-CRP levels were positively correlated with urine fluoride levels (r = 0.36, p < 0.001). We have found that plasma neopterin and hs-CRP levels are increased in patients with endemic fluorosis. We have concluded that inflammation play an important role in the pathophysiology of fluoride toxicity in patients with endemic fluorosis.

The relationship of PTH Bst BI polymorphism, calciotropic hormone levels, and dental fluorosis of children in China.

The aim of this study was to explore the association of parathyroid hormone (PTH) gene Bst BI polymorphism, calciotropic hormone levels, and dental fluorosis of children. A case-control study was conducted in two counties (Kaifeng and Tongxu) in Henan Province, China in 2005-2006. Two hundred and twenty-five children were recruited and divided into three groups including dental fluorosis group (DFG), non-dental fluorosis group (NDFG) from high fluoride areas, and control group (CG). Urine fluoride content was determined using fluoride ion selective electrode; PTH Bst BI were genotyped using PCR-RFLP; osteocalcin (OC) and calcitonin (CT) levels in serum were detected using radioimmunoassay. Genotype distributions were BB 85.3% (58/68), Bb 14.7% (10/68) for DFG; BB 77.6% (52/67), Bb 22.4% (15/67) for NDFG; and BB 73.3% (66/90), Bb 27.7% (24/90) for CG. No significant difference of Bst BI genotypes was observed among three groups (P > 0.05). Serum OC and urine fluoride of children were both significantly higher in DFG and NDFG than in CG (P < 0.05, respectively), while a similar situation was not observed between DFG and NDFG in high fluoride areas (P > 0.05). Serum OC level of children with BB genotype was significantly higher compared to those with Bb genotype in high fluoride areas (P < 0.05). However, no significant difference of serum CT or calcium (Ca) was observed. In conclusion, there is no correlation between dental fluorosis and PTH Bst BI polymorphism. Serum OC might be a more sensitive biomarker for detecting early stages of dental fluorosis, and further studies are needed.

[Study on the association between environmental chemical elements and fluorosis caused by coal-fire pollution].

OBJECTIVE: To understand the distribution of chemical elements in soil. To investigate the differences between patients under different state of fluorosis and normal population after preventive measurement was implemented to get rid of some chemical elements and to lower the urine fluoride levels so as to illustrate the pathogenesis of the disease. METHODS: Both ecological and comparative studies had been used to analyze the rates and levels of chemical elements. Teeth and skeletal from the patients with fluorosis and controls were taken and florin ion-selective-electrode method was used to determine urine the content of fluorine. Atomic Absorption Spectrometry was used to determine the copper, zinc, calcium, magnesium and iron contents in the whole blood. Differences of contents were analyzed. RESULTS: In Wushan county, the soil contents of nickel (r = 0.553, P = 0.050), iodine (r = 0.571, P = 0.041), fluorine (r = 0.303, P = 0.005), pH value (r = 0.304, P = 0.005) and the rates of fluorosis showed weaker positive relationship. In Fengjie county, the soil contents of mercury (r = 0.285, P = 0.001), nickel (r = 0.212, P = 0.00) and the rates of fluorosis also showed weaker positive relationship. In Wushan county, the urine fluoride level in the patients group [(0.64 ± 0.34) mg/L] was higher than that in the control group [(0.44 ± 0.59) mg/L], (P < 0.05). In Fengjie county, copper [(29.63 ± 3.32) µmol/L] and urine fluoride [(0.83 ± 0.37) mg/L] levels in the patients group showed higher than that in the control group [(26.76 ± 3.63) µmol/L, (0.53 ± 0.23) mg/L], (P < 0.05). zinc (Zn) [(76.13 ± 11.24) µmol/L], calcium (Ca) [(1.87 ± 0.25) mmol/L], magnesium (Mg) [(1.41 ± 0.18) mmol/L] and fluoride[(0.83 ± 0.37) mg/L]levels in urine of the patients in children were higher in Fengjie than that in Wushan [(71.95 ± 7.53) µmol/L, (1.43 ± 1.34) mmol/L, (1.34 ± 0.15) mmol/L, (0.64 ± 0.34) mg/L], (P < 0.05). Mg [(1.56 ± 1.96) mmol/L], ferrum [(8.15 ± 1.00) mmol/L] and fluoride [(2.17 ± 0.99) mg/L] levels among adult patients were significantly higher than in the control group [(1.46 ± 0.16) mmol/L, (7.64 ± 1.00) mmol/L, (1.44 ± 1.22) mg/L] (P < 0.05). CONCLUSION: Soil, rich in alkaline and fluorosis could increase the intake of fluorine while nickel, cadmium, iodine content in soil might relate to the occurrence of fluorosis. Residents living in endemic areas where anti-fluorine elements as Zn, Ca and Mg were in shortage, might be affected by these chemical elements that related with fluorosis.

Influence of selenium and fluoride on blood antioxidant capacity of rats.

This study is to explore the effect of selenium and fluoride on blood antioxidant capacity of rats, and try to find out the optimal level of selenium in drinking water against fluorosis. Animals were divided into control group, sodium fluoride treated group (NaF, 50 mg/L) and selenium+NaF treated group (sodium selenite 0.375, 0.75, 1.5 mg/L) in water were respectively administered to male rats, which were decapitated after 6 months. Their blood was collected for GSH-Px activity, plasma SOD activity, T-AOC assay, uric acid assay, sialic acid (SA) content and MDA content, and the fluidity of erythrocyte membrane by electron spin resonance (ESR) was analyzed. The results showed that, compared with the control group, the blood antioxidant capacity of the rats exposed to fluoride was down-regulated significantly (P<0.05, P<0.01), MDA content increased significantly (P<0.05), the fluidity of erythrocyte membrane decreased (P<0.05, P<0.01). Meanwhile, the treatments of selenium along with NaF compared with fluorosis group, SOD activity, GSH-Px activity and T-AOC assay increased respectively, MDA content decreased significantly (P<0.05) in NaF+Se (Se 0.75, 1.5 mg/L) treated groups, uric acid level was up-regulated, but had no statistical significant difference (P>0.05). The fluidity of erythrocyte membrane showed significant increase (P<0.05), the content of SA was lower. Fluorosis could induce the decline of blood antioxidant capacity and the fluidity of erythrocyte membrane, as evident in this study, and Se at different levels possess some antagonistic effects on blood induced by fluoride. However, high dose of selenium (1.5 mg/L) is the optimum concentration.

Phenotypic variation of fluoride responses between inbred strains of mice.

Excessive systemic exposure to fluoride (F) can lead to disturbances in bone homeostasis and dental enamel development. We have previously shown strain-specific responses to F in the development of dental fluorosis (DF) and in bone formation/mineralization. The current study was undertaken to further investigate F responsive variations in bone metabolism and to determine possible relationships with DF susceptibility. Seven-week-old male mice from FVB/NJ, C57BL/6J, C3H/HeJ, A/J, 129S1/SvImJ, AKR/J, DBA/2J, and BALB/cByJ inbred strains were exposed to NaF (0 or 50 ppm as F(-)) in drinking water for 60 days. Sera were collected for F, Ca, Mg, PO(4), iPTH, sRANKL, and ALP levels. Bone marrow cells were subjected to ex vivo cell culture for osteoclast potential and CFU colony assays (CFU-fibroblast, CFU-osteoblast, CFU-erythrocyte/granulocyte/macrophage/megakaryocyte, CFU-granulocyte/macrophage, CFU-macrophage, and CFU-granulocyte). Femurs and vertebrae were subjected to micro-CT analyses, biomechanical testing, and F, Mg, and Ca content assays. DF was evaluated using quantitative fluorescence and clinical criteria. Strain-specific responses to F were observed for DF, serum studies, ex vivo cell culture studies, and bone quality. Among the strains, there were no patterns or significant correlations between DF severity and the actions of F on bone homeostasis (serum studies, ex vivo assays, or bone quality parameters). The genetic background continues to play a role in the actions of F on tooth enamel development and bone homeostasis. F exposure led to variable phenotypic responses between strains involving dental enamel development and bone metabolism.

Study on blood biochemical diagnostic indices for hepatic function biomarkers in endemic skeletal fluorosis.

The aim of the study was to determine the relationship of fluoride in drinking water to liver function in individuals living in normal and seven endemic fluorosis areas of Punjab, India. The concentration of fluoride in drinking water of different areas varied from 5.9 to 24.5 mg/L. Study group consisted of 705 patients in the age group between 20 and 60 years (mean age of 39.35±11.27) affected with osteodental fluorosis were compared with 300 age- and sex-matched controls (with mean age of 35.28±8.25 years). Biochemical data was analyzed by one-way analysis of variance (ANOVA) with post hoc Tukey-Kramer and Bonferroni multiple comparison tests. The relationship between hepatic enzymes was calculated by Pearson's correlation and linear regression. The results revealed significantly (P<0.001) higher concentration of serum fluoride in patients when compared to control. The mean activities of cyclic adenosine monophosphate (AMP), alkaline phosphatase (ALKP), acid phosphatase (ACP), aspartate aminotransaminase (AST), and alanine aminotransaminase (ALT) were significantly (P<0.05-0.001) elevated in patients from all fluoride areas. ANOVA with post hoc Turkey-Kramer and Bonferroni multiple comparison test demonstrated a significant (P<0.0001) variance in the activities of cAMP, ALKP, ACP, AST, and ALT in fluorotic patients, with elevation in water fluoride levels. Maximum elevation of 196.14% (ACP), 99.31% (cyclic adenosine monophosphate; cAMP), 72.08% (ALT), 60.14% (AST), and least 21.35% (ALKP) was recorded in patients exposed to 24.5 mg/L fluoride in drinking water. There was positive correlation between water fluoride, serum fluoride and AST (r=0.77, 0.91), ALT (r=0.82, 0.90), ALKP (r=0.88, 0.97), and ACP (r=0.74, 0.85). Pearson's correlation demonstrated highly significant (P<0.05) positive relationship between water fluoride and cAMP (regression equation: Y=0.9807×+22:081, =0.84; r=0.92, P<0.05). The increased levels of transaminases in fluorotic patients suggest alteration in liver functions. The level of alkaline and acid phosphatase was increased during fluoride intoxication which is also an early marker of hepatic cell damage because of its specificity and catalytic activity. The elevated levels of enzymes are reflective of bone disorders, which are characterized by increased osteoblastic activity. There levels increased several times if cellular damage occurs in the liver. The results suggest that fluoride exposure intensifies the activities of hepatic function enzymes in osteofluorosis.

Serum copper, zinc, and magnesium levels in patients with chronic fluorosis.

Although there are many studies on effect of fluoride on trace elements in experimental animals, few studies exist on serum trace elements levels in patients with endemic fluorosis. We aimed to determine the serum levels of trace elements including serum copper (Cu), zinc (Zn), and serum levels of minerals including calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na), potassium (K) in patients with endemic fluorosis. The study group consisted of 30 patients with endemic fluorosis (17 females, 13 males, mean age 33.53±9.85 years). An age, gender, and body mass index matched 30 healthy volunteers comprised control group (21 females, ten males with a mean age 33.93±7.39 years). Urine fluoride levels of chronic fluorosis patients were significantly higher than that of control subjects as expected (1.92±0.10 mg/l vs. 0.41±0.09 mg/l, respectively; P<0.001). Serum Cu levels (89.14±16.77 µg/dL vs. 102.69±25.04 µg/dL, respectively, P=0.017), serum Zn levels (77.98±20.58 µg/dL vs. 94.57±35.87µg/dL, respectively, P=0.032), and serum Mg levels (1.92±0.18 mg/dL vs. 2.07±0.31 mg/dL, respectively, p=0.022) was significantly lower in chronic fluorosis patients than in controls. There were no statistically significant differences between the fluorosis group and control group with respect to serum levels of Na, K, Ca, and P. We concluded that chronic fluorosis is associated with reduced serum levels of Cu, Zn, and Mg.

Effect of endemic fluorosis on hematological parameters.

Although so many studies exist on effect of fluoride on hematological parameters in experimental animals, a few studies have been conducted to investigate the effects of chronic fluorosis on hematological parameters in humans' subjects with endemic fluorosis. So we aimed to determine the hematological parameters in patients with endemic fluorosis. The study group consisted of 60 patients with endemic fluorosis (27 females, 33 males, and mean age 33.4 ± 9.6 years). An age-, gender-, and body mass index-matched control group was composed of 34 healthy volunteers (11 females, 23 males with a mean age 32.6 ± 5.6 years). Urine fluoride levels of fluorosis patients were significantly higher than control subjects as expected (0.42 ± 0.09 vs 1.92 ± 0.14 mg/l, respectively; P < 0.001). There were no statistically significant differences between the fluorosis group and control group with respect to hematological parameters (complete blood count and ferritin). We concluded that chronic fluorosis has no effect on hematological parameters in patients with endemic fluorosis.

The association between osteocalcin gene polymorphism and dental fluorosis among children exposed to fluoride in People's Republic of China.

Excessive fluoride intake has been shown to affect dentin and cementum mineralization throughout life. Some studies indicated that a HindIII polymorphism, of osteocalcin (OC) gene, was associated with bone metabolism-related diseases. Therefore, it is possible that the variation in OC genotypes will be associated with dental fluorosis (DF) status and/or serum caciotropic hormone level. A case-control study was conducted among children aged 8-12 years in Henan Province, PR China to investigate the association between dental fluorosis, serum calciotropic hormone level, and polymorphisms in the OC gene. HindIII polymorphism in OC gene was genotyped using the PCR-RFLP procedure. OC and calcitonin (CT) level in serum was detected using radioimmunoassay. No significant difference was observed for OC HindIII genotypes among the cases with dental fluorosis, the controls from endemic fluorosis area (EFA) and the controls from non-endemic fluorosis area (NEFA). A significant negative correlation was observed between serum calcium and OC level. No significant relationship was found between OC HindIII polymorphisms and the level of OC and CT. In conclusion, OC HindIII polymorphisms may not be a useful genetic marker for differential risk of dental fluorosis among children in PR China.

COL1A2 gene polymorphisms (Pvu II and Rsa I), serum calciotropic hormone levels, and dental fluorosis.

OBJECTIVES: To investigate the relationship between dental fluorosis, polymorphisms in the COL1A2 gene, and serum calciotropic hormone levels. METHODS: We conducted a case-control study among children between 8 and 12 years of age with (n = 75) and without (n = 165) dental fluorosis in two counties in Henan Province, China. The PvuII and RsaI polymorphisms in the COL1A2 gene were genotyped using the PCR-RFLP procedure. Calcitonin and osteocalcin levels in the serum were measured using radioimmunassays. RESULTS: Children carrying the homozygous genotype PP of COL1A2 PvuII had a significantly increased risk of dental fluorosis (OR =4.85, 95% CI: 1.22-19.32) compared to children carrying the homozygous genotype pp in an endemic fluorosis village (EFV). However, the risk (OR = 1.07, 95% CI: 0.45-2.52) was not elevated when the control population was recruited from a non-endemic fluorosis village. Additionally, fluoride levels in urine and osteocalcin levels in serum were found to be significantly lower in controls from non-endemic villages compared to cases. However, the differences in fluoride and osteocalcin levels were not observed when cases were compared to a control population from endemic fluorosis villages. CONCLUSIONS: This study provides the first evidence of an association between polymorphisms in the COL1A2 gene with dental fluorosis in high fluoride exposed populations. Future studies are needed to confirm the association.