Association of PPARGC1A gene polymorphism and mtDNA methylation with coal-burning fluorosis: a case–control study
Juhui Song,
Ansu Zhao,
Ruichao Li,
Yunyan Luo,
Yangting Dong,
Chanjuan Wang,
Ting Zhang,
Jie Deng,
Xiaolan Qi,
Zhizhong Guan,
Yan He
Affiliations
Juhui Song
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, & Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University
Ansu Zhao
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, & Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University
Ruichao Li
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, & Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University
Yunyan Luo
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, & Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University
Yangting Dong
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, & Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University
Chanjuan Wang
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, & Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University
Ting Zhang
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, & Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University
Jie Deng
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, & Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University
Xiaolan Qi
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, & Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University
Zhizhong Guan
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, & Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University
Yan He
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, & Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry, Guizhou Medical University
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 < 0.001; χ 2 = 21.198, P < 0.001; χ 2 = 36.078, P < 0.001). Conclusion PPARGC1A polymorphisms rs13131226 and rs1873532 and the mitochondrial DNA D-loop methylation site CpG_4 have been associated with an increased risk of fluorosis, conversely polymorphism rs7665116 was associated with a decreased risk of fluorosis. Polymorphisms rs2970870 were associated with increased risk of skeletal fluorosis, and polymorphism rs2970847 was associated with decreased risk of skeletal fluorosis. These SNPs and CpG can be used as potential targets to assess fluorosis risk.
