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Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
Interaction between fluoride exposure and bone metabolism-related gene polymorphisms in the susceptibility to
Yue Gao1, Qingbo Wang1, Shuaifei Yang1
1Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150086, PR China; NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin 150086, PR China; Joint Key Laboratory of Endemic Diseases, Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University, PR China.
Background:
Groundwater contaminated with high fluoride levels poses a global public health concern. While fluoride exposure has been linked to hypertension, the role of genetic polymorphisms in bone metabolism-related genes in modulating this relationship remains unclear.
Objective:
This study aimed to investigate the associations between fluoride exposure, polymorphisms in bone metabolism-related genes, and susceptibility to essential hypertension in a Han Chinese population.
Methods:
A cross-sectional study was conducted involving 837 participants (424 hypertension cases and 413 controls) from endemic fluorosis areas in China. Bayesian benchmark dose (BBMD) modeling was applied to estimate the dose-response relationship between fluoride exposure and hypertension. Multivariable logistic regression was used to evaluate associations between hypertension and single nucleotide polymorphisms (SNPs) in four genes: COL11A1 (rs2615977), LRP5 (rs3736228), SMAD3 (rs12901499), and ANP32A (rs7164503). Generalized multifactor dimensionality reduction (GMDR) was employed to assess gene-gene and gene-environment interactions.
Results:
Urinary fluoride (UF) was significantly associated with increased risk of hypertension (OR = 1.371, 95% CI: 1.164-1.614). BBMD analysis yielded BMD and BMDL values of 0.36 mg/L and 0.21 mg/L, respectively, at a BMR level of 5%. Certain SNPs showed significant associations in stratified subgroups. The rs2615977 AC+CC genotype was associated with increased hypertension risk in older, male, high-fluoride, and lean individuals, whereas LRP5 rs3736228 TC+TT and SMAD3 rs12901499 AG+GG genotypes conferred protective effects in specific exposure and demographic subgroups. Additionally, the ANP32A rs7164503 TC genotype was linked to reduced risk among females, high-fluoride, and lean participants. Notably, a four-locus gene-gene interaction model (COL11A1 × LRP5 × SMAD3 × ANP32A) demonstrated significant effects on hypertension susceptibility (testing balanced accuracy = 0.5931; cross-validation consistency = 10/10; P = 0.0107).
Conclusions:
This study suggests an association between fluoride exposure and hypertension, and indicates that bone metabolism-related genetic polymorphisms may modify this association. These findings provide novel insights into the gene-environment interplay in fluoride-induced hypertension and highlight potential targets for precision prevention.
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