Association between polymorphism and haplotype of ATP2B1 gene and skeletal fluorosis in Han population

To evaluate the association between ATP2B1 gene polymorphisms and skeletal fluorosis, a cross-sectional study was conducted. In China, 962 individuals were recruited, including 342 cases of skeletal fluorosis. Four TP2BA1 polymorphisms (rs2070759, rs12817819, rs17249754, and rs7136259) were analysed. The results suggested that rs17249754 and rs7136259 were associated with skeletal fluorosis. After controlling confounders, the protective effect of GG genotype in rs17249754 was apparent in individuals over 45 years old, female, with urine fluoride concentration below 1.6 mg/L, serum calcium above 2.25 mmol/L or serum phosphorus between 1.1 and 1.3. Heterozygote TC in rs7136259 increased the risk of skeletal fluorosis in subjects who are elderly, female, with urinary fluoride more than 1.6 mg/L, serum calcium more than 2.25 mmol/L and blood phosphorus between 1.1 and 1.3 mmol/L. Four loci were found to be tightly related by linkage disequilibrium analysis, and the frequency of distribution of haplotype GCGT was lower in the skeletal fluorosis group.

Automated summary

This cross-sectional study evaluated the association between ATP2B1 gene polymorphisms and skeletal fluorosis. A total of 962 individuals, including 342 cases of skeletal fluorosis, were recruited in China. Four TP2BA1 polymorphisms (rs2070759, rs12817819, rs17249754, and rs7136259) were analyzed. The results indicated that rs17249754 and rs7136259 were associated with skeletal fluorosis. After controlling for confounders, the GG genotype of rs17249754 showed a protective effect in individuals aged over 45, female, with urine fluoride concentration below 1.6 mg/L, serum calcium above 2.25 mmol/L, or serum phosphorus between 1.1 and 1.3. The heterozygote TC of rs7136259 increased the risk of skeletal fluorosis in elderly, female subjects with urinary fluoride concentration above 1.6 mg/L, serum calcium above 2.25 mmol/L, and blood phosphorus between 1.1 and 1.3 mmol/L. Linkage disequilibrium analysis revealed a tight relationship among the four loci, and the distribution frequency of haplotype GCGT was lower in the skeletal fluorosis group.