LDL receptor-related protein 5 rs648438 polymorphism is associated with the risk of skeletal fluorosis.

To investigate the potential association between LRP5 rs648438 polymorphism and the risk of skeletal fluorosis (SF) was evaluated in a cross-sectional case-control study conducted in Shanxi, China, in 2019. A total of 973 individuals were enrolled in this study, in which cases and controls were 346 and 627, respectively. SF was diagnosed according to the standard WS/192-2008 (China). The LRP5 rs648438 was detected by the multiple PCR and sequencing. LRP5 rs648438 was found to follow a dominant genetic model using a web-based SNP-STATS software. Logistic regression analysis found that the TC/CC genotype of LRP5 rs648438 might be a protective factor for SF. When stratified by gender, this protective effect of TC/CC genotype in rs648438 was pronounced in males. There was an interaction between gender and rs648438 on risk of SF. Our study suggested that TC/CC genotype of rs648438 might be a protective factor for water-drinking-type skeletal fluorosis, especially in male participants.

[1]  Susanna Balcells,et al.  Wnt Pathway Extracellular Components and Their Essential Roles in Bone Homeostasis , 2022, Genes.

[2]  Jing Han,et al.  Progress of Signaling Pathways, Stress Pathways and Epigenetics in the Pathogenesis of Skeletal Fluorosis , 2021, International journal of molecular sciences.

[3]  A. Zhang,et al.  let-7c-5p regulates CyclinD1 in fluoride-mediated osteoblast proliferation and activation. , 2021, Toxicological Sciences.

[4]  Wei Huang,et al.  Association between Bone Morphogenetic Protein 2 Gene Polymorphisms and Skeletal Fluorosis of The Brick-tea Type Fluorosis in Tibetans and Kazakhs, China , 2021, International journal of environmental health research.

[5]  Zaihong Zhang,et al.  sKlotho is associated with the severity of brick tea-type skeletal fluorosis in China. , 2020, The Science of the total environment.

[6]  W. Gu,et al.  β-catenin mediates fluoride-induced aberrant osteoblasts activity and osteogenesis. , 2020, Environmental pollution.

[7]  S. Flora,et al.  Fluoride in Drinking Water and Skeletal Fluorosis: a Review of the Global Impact , 2020, Current Environmental Health Reports.

[8]  Yasuhiro Kobayashi,et al.  The Regulation of Bone Metabolism and Disorders by Wnt Signaling , 2019, International journal of molecular sciences.

[9]  D. Q. Tri,et al.  Fluoride contamination, health problems and remediation methods in Asian groundwater: A comprehensive review. , 2019, Ecotoxicology and environmental safety.

[10]  Wei Huang,et al.  Association between ALOX15 gene polymorphism and brick-tea type skeletal fluorosis in Tibetans, Kazaks and Han, China , 2019, International journal of environmental health research.

[11]  H. Riahi,et al.  Skeletal fluorosis: don’t miss the diagnosis! , 2019, Skeletal Radiology.

[12]  R. Chandrajith,et al.  Groundwater fluoride in Sri Lanka: opportunities to mitigate the risk at maximum contaminant level , 2018, Ceylon Medical Journal.

[13]  X. S. Liu,et al.  Effects of reproduction on sexual dimorphisms in rat bone mechanics. , 2018, Journal of biomechanics.

[14]  Yumei Fan,et al.  FRZB1 rs2242070 polymorphisms is associated with brick tea type skeletal fluorosis in Kazakhs, but not in Tibetans, China , 2018, Archives of Toxicology.

[15]  R. Rizzoli,et al.  Interaction between LRP5 and periostin gene polymorphisms on serum periostin levels and cortical bone microstructure , 2018, Osteoporosis International.

[16]  M. Mansournia,et al.  Prediction of age at menopause in women with polycystic ovary syndrome , 2018, Climacteric : the journal of the International Menopause Society.

[17]  S. Pramanik,et al.  The genetic influence in fluorosis. , 2017, Environmental toxicology and pharmacology.

[18]  Qing Yang,et al.  Matrix Metallopeptidase-2 Gene rs2287074 Polymorphism is Associated with Brick Tea Skeletal Fluorosis in Tibetans and Kazaks, China , 2017, Scientific Reports.

[19]  Ying Wang,et al.  Two novel susceptibility loci for non-small cell lung cancer map to low-density lipoprotein receptor-related protein 5 , 2016, Oncology letters.

[20]  S. Shekhar,et al.  Worldwide contamination of water by fluoride , 2016, Environmental Chemistry Letters.

[21]  L. Heidari,et al.  Osteoporosis: A Silent Disease with Complex Genetic Contribution. , 2016, Journal of genetics and genomics = Yi chuan xue bao.

[22]  R. Chapurlat,et al.  Serum periostin is associated with fracture risk in postmenopausal women: a 7-year prospective analysis of the OFELY study. , 2014, The Journal of clinical endocrinology and metabolism.

[23]  Xiaoying Guo,et al.  Fluoride promotes osteoblastic differentiation through canonical Wnt/β-catenin signaling pathway. , 2014, Toxicology letters.

[24]  J. Pei,et al.  Myeloperoxidase Activity and Its Corresponding mRNA Expression as well as Gene Polymorphism in the Population Living in the Coal-Burning Endemic Fluorosis Area in Guizhou of China , 2013, Biological Trace Element Research.

[25]  J. Marc,et al.  Analysis of Association of LRP5, LRP6, SOST, DKK1, and CTNNB1 Genes with Bone Mineral Density in a Slovenian Population , 2009, Calcified Tissue International.

[26]  M. Bhatnagar,et al.  Physiology and toxicity of fluoride. , 2009, Indian journal of dental research : official publication of Indian Society for Dental Research.

[27]  J. Kaufman,et al.  Genome-wide linkage screen of bone mineral density (BMD) in European pedigrees ascertained through a male relative with low BMD values: evidence for quantitative trait loci on 17q21-23, 11q12-13, 13q12-14, and 22q11. , 2008, The Journal of clinical endocrinology and metabolism.

[28]  G. Karsenty,et al.  In vivo analysis of Wnt signaling in bone. , 2007, Endocrinology.

[29]  E. Everett,et al.  Dental Fluorosis: Variability among Different Inbred Mouse Strains , 2002, Journal of dental research.

[30]  Ivan Lobov,et al.  Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor , 2002, The Journal of cell biology.

[31]  P. DenBesten Biological mechanisms of dental fluorosis relevant to the use of fluoride supplements. , 1999, Community dentistry and oral epidemiology.