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, Guiyang, Guizhou, China.
Department of Laboratory Medicine, Guangzhou Panyu Central Hospital, Guangzhou, China.
BMC Genomics. 2024 Sep 30;25(1):908. doi: 10.1186/s12864-024-10819-9.
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.
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 = 16.917, P < 0.001; χ = 21.198, P < 0.001; χ = 36.078, P < 0.001).
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.
燃煤型氟中毒是由于长期使用当地高氟煤进行取暖和烹饪而导致的慢性中毒。研究表明，长期暴露于氟化物会降低 PPARGC1A 水平。因此，本病例对照研究旨在评估 PPARGC1A 基因多态性和线粒体 D-环区甲基化与燃煤型氟中毒的遗传关联。
rs13131226 的 TT 基因型和 rs1873532 的 AA 基因型增加了燃煤氟中毒的风险（OR=1.84，P=0.004；OR=1.97，P=0.007），rs7665116 的 CT 和 CC 基因型降低了燃煤氟中毒的风险（OR=0.54，P=0.003）。rs2970847 位点的 TT 基因型和 rs2970870 位点的 AA 基因型增加了发生氟骨症的风险（OR=4.12，P=0.003；OR=2.22，P=0.011）。由 rs3736265-rs1873532 构建的 AG 单倍型增加了燃煤氟中毒流行的风险（OR=1.465，P=0.005）；CG 降低了燃煤氟中毒流行的风险（OR=0.726，P=0.020）。由 rs6821591-rs768695-rs3736265-rs2970847 构建的 CGGT 单倍型增加了氟骨症流行的风险（OR=1.558，P=0.027）。mtDNA D-环区 CpG_4 甲基化水平增加 1%，燃煤氟中毒的风险增加 2.3%。此外，在贵州人群中观察到 rs13131226 与 rs1873532、CpG_4 与 CpG_8.9、rs13131224、rs6821591 和 rs7665116 之间存在显著的交互作用（χ²=16.917，P<0.001；χ²=21.198，P<0.001；χ²=36.078，P<0.001）。
PPARGC1A 多态性 rs13131226 和 rs1873532 以及线粒体 DNA D-环区 CpG_4 甲基化与氟中毒风险增加相关，相反，多态性 rs7665116 与氟中毒风险降低相关。rs2970870 多态性与氟骨症风险增加相关，rs2970847 多态性与氟骨症风险降低相关。这些 SNP 和 CpG 可以作为评估氟中毒风险的潜在靶点。
