Association of PPARGC1A gene polymorphism and mtDNA methylation with coal-burning fluorosis: a case–control study

Abstract Background Coal-burning fluorosis is a chronic poisoning resulting from the prolonged use of locally available high-fluoride coal for heating and cooking. Prolonged fluoride exposure has been demonstrated to decrease PPARGC1A levels. Therefore, this case-control aims to evaluate the genetic association of PPARGC1A gene polymorphisms and methylation of the mitochondrial D-loop region with coal-burning fluorosis. Result The results showed that the TT genotype at rs13131226 and the AA genotype at rs1873532 increased the risk of coal-burning fluorosis (OR = 1.84, P = 0.004; OR = 1.97, P = 0.007), the CT and CC genotypes at rs7665116 decreased the risk of coal-burning fluorosis (OR = 0.54, P = 0.003). The TT genotype at the rs2970847 site and the AA genotype at the rs2970870 site increase the risk of developing skeletal fluorosis (OR = 4.12, P = 0.003; OR = 2.22, P = 0.011). Haplotype AG constructed by rs3736265-rs1873532 increased the risk of the prevalence of coal-burning fluorosis (OR = 1.465, P = 0.005); CG decreased the risk of the prevalence of coal-burning fluorosis (OR = 0.726, P = 0.020). Haplotype CGGT constructed by rs6821591-rs768695-rs3736265-rs2970847 increased the risk of the prevalence of skeletal fluorosis (OR = 1.558, P = 0.027). A 1% increase in CpG_4 methylation levels in the mtDNA D-loop region is associated with a 2.3% increase in the risk of coal-burning fluorosis. Additionally. There was a significant interaction between rs13131226 and rs1873532; CpG_4 and CpG_8.9; rs13131224,rs6821591 and rs7665116 were observed in the occurrence of fluorosis in the Guizhou population (χ 2 = 16.917, P