Abstract
Close to 12 million people in India are affected by more than the desirable level of fluoride in drinking water that could lead to dental, skeletal, and non-skeletal fluorosis. Dental fluorosis is a developmental defect that results in hypo-mineralization and pronounced porosity of enamel in the affected individuals. As estrogen receptor 1 (ESR1), collagen type 1 alpha 2 (COL1A2), bone γ-carboxyglutamic acid protein (BGLAP), and secreted protein acidic and cysteine rich (SPARC) genes are involved in bone development and mineralization, polymorphisms in these genes could be determining factors in influencing the risk to fluorosis among the exposed individuals in fluoride endemic areas. A case-control study was carried out among a total of 87 individuals (case = 36, control = 51) to examine the association between selected polymorphisms in the ESR1, COL1A2, BGLAP, and SPARC genes and risk of dental fluorosis from a fluoride endemic region of Eastern India. Altogether, 10 single nucleotide polymorphisms (SNPs) in ESR1 (rs2234693, rs2228480, rs3798577, rs2077647, and rs9340799), COL1A2 (rs42524, rs412777), BGLAP (rs1800247), and SPARC (rs6579885, rs4958278) genes were genotyped through PCR-RFLP in these subjects. The association of the SNPs for disease risk estimation was measured by odds ratio with 95% confidence interval. The risk genotypes of none of the 10 SNPs showed statistically significant association with risk of dental fluorosis. Frequencies of the haplotypes in the intragenic SNPs of the ESR1, COL1A2, and SPARC genes did not reveal any statistically significant difference between the case and control groups. The present study is the first of its kind from India that has attempted to investigate possible involvement of genetic factors in influencing the risk to fluorosis among the population from a fluoride endemic region.
Similar content being viewed by others
References
Grynpas MD, Chachra D, Limeback H (2000) The action of fluoride on bone. In: The action of fluoride on bone. Cambridge University Press
Meenakshi RC (2006) Fluoride in drinking water and its removal. J Hazard Mater 137:456–463
Fomon SJ, Ekstrand J, Ziegler EE (2000) Fluoride intake and prevalence of dental fluorosis: trends in fluoride intake with special attention to infants. J Public Health Dent 60:131–139
DenBesten P, Li W (2011) Chronic fluoride toxicity: dental fluorosis. Monogr Oral Sci 22:81–96
Susheela AK (1999) Fluorosis management programme in India. Curr Sci 77:1250–1256
Saravanan S, Kalyani C, Vijayarani M et al (2008) Prevalence of dental fluorosis among primary school children in rural areas of Chidambaram taluk, Cuddalore district, Tamil Nadu. Indian J Community Med 33:146–150
Shortt HE, Pandit CG, Raghavachari RSTNS (1937) Endemic fluorosis in the Nellore District of South India. Ind Med Gaz 72:396–398
Majumdar KK (2011) Health impact of supplying safe drinking water containing fluoride below permissible level on flourosis patients in a fluoride-endemic rural area of West Bengal. Indian J Public Health 55:303–308
Pramanik S, Saha D (2017) The genetic influence in fluorosis. Environ Toxicol Pharmacol 56:157–162
Kuchler EC, Dea Bruzamolin C, Ayumi Omori M et al (2018) Polymorphisms in nonamelogenin enamel matrix genes are associated with dental fluorosis. Caries Res 52:1–6
Jiang M, Mu L, Wang Y, Yan W, Jiao Y (2015) The relationship between Alu I polymorphisms in the calcitonin receptor gene and fluorosis endemic to Chongqing, China. Med Princ Pract 24:80–83
Huang H, Ba Y, Cui L, Cheng X, Zhu J, Zhang Y, Yan P, Zhu C, Kilfoy B, Zhang Y (2008) COL1A2 gene polymorphisms (Pvu II and Rsa I), serum calciotropic hormone levels, and dental fluorosis. Community Dent Oral Epidemiol 36:517–522
Scheven BA, Damen CA, Hamilton NJ et al (1992) Stimulatory effects of estrogen and progesterone on proliferation and differentiation of normal human osteoblast-like cells in vitro. Biochem Biophys Res Commun 186:54–60
Xie J, Wang S, He B, Pan Y, Li Y, Zeng Q, Jiang H, Chen J (2009) Association of estrogen receptor alpha and interleukin-10 gene polymorphisms with endometriosis in a Chinese population. Fertil Steril 92:54–60
Phillips CL, Bradley DA, Schlotzhauer CL et al (2000) Oim mice exhibit altered femur and incisor mineral composition and decreased bone mineral density. Bone 27:219–226
Suuriniemi M, Mahonen A, Kovanen V et al (2003) Relation of PvuII site polymorphism in the COL1A2 gene to the risk of fractures in prepubertal Finnish girls. Physiol Genomics 14:217–224
Willing MC, Torner JC, Burns TL, Janz KF, Marshall T, Gilmore J, Deschenes SP, Warren JJ, Levy SM (2003) Gene polymorphisms, bone mineral density and bone mineral content in young children: the Iowa bone development study. Osteoporos Int 14:650–658
Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047
Price PA, Parthemore JG, Deftos LJ (1980) New biochemical marker for bone metabolism. Measurement by radioimmunoassay of bone GLA protein in the plasma of normal subjects and patients with bone disease. J Clin Invest 66:878–883
Deng HW, Shen H, Xu FH, Deng HY, Conway T, Zhang HT, Recker RR (2002) Tests of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density. J Bone Miner Res 17:678–686
Delany AM, McMahon DJ, Powell JS, Greenberg DA, Kurland ES (2008) Osteonectin/SPARC polymorphisms in Caucasian men with idiopathic osteoporosis. Osteoporos Int 19:969–978
Susheela AK (1991) Prevention and control of fluorosis: dental fluorosis-symptoms, 1st edn. National Technology Mission on Drinking Water, New Delhi, pp 7–9
Choubisa SL (2001) Endemic Fluorosuis in southern Rajasthan, India. Fluoride 34:61–70
Isaac A, Wilma Delphine Silvia CR, Somanna SN et al (2009) Prevalence and manifestations of water borne fluorosis among school children in Kaiwara village of India: a preliminary study. Asian Biomed 3:563–566
Kumar S, Lata S, Yadav J et al (2016) Relationship between water, urine and serum fluoride and fluorosis in school children of Jhajjar District, Haryana, India. Appl Water Sci 7:3377–3384
Srivastava RN, Gill DS, Moudgil A, Menon RK, Thomas M, Dandona P (1989) Normal ionized calcium, parathyroid hypersecretion, and elevated osteocalcin in a family with fluorosis. Metabolism 38:120–124
Singh N, Verma KG, Verma P et al (2014) A comparative study of fluoride ingestion levels, serum thyroid hormone & TSH level derangements, dental fluorosis status among school children from endemic and non-endemic fluorosis areas. Springerplus 3:7
Indian Genome Variation Consortium (2008) Genetic landscape of the people of India: a canvas for disease gene exploration. J Genet 87:3–20
Michel-Crosato E, Biazevic MG, Crosato E (2005) Relationship between dental fluorosis and quality of life: a population based study. Braz Oral Res 19:150–155
Ba Y, Zhang H, Wang G, Wen S, Yang Y, Zhu J, Ren L, Yang R, Zhu C, Li H, Cheng X, Cui L (2011) Association of dental fluorosis with polymorphisms of estrogen receptor gene in Chinese children. Biol Trace Elem Res 143:87–96
Abbasi S, Ismail P, Azimi C et al (2011) rs2228480 polymorphism in ESR1 gene and risk of breast cancer. Payavard 8:478–491
Fernandez LP, Milne RL, Barroso E et al (2006) Estrogen and progesterone receptor gene polymorphisms and sporadic breast cancer risk: a Spanish case-control study. Int J Cancer 119:467–471
Zhang L, Gu L, Qian B, Hao X, Zhang W, Wei Q, Chen K (2009) Association of genetic polymorphisms of ER-alpha and the estradiol-synthesizing enzyme genes CYP17 and CYP19 with breast cancer risk in Chinese women. Breast Cancer Res Treat 114:327–338
Escobar-Garcia D, Mejia-Saavedra J, Jarquin-Yanez L et al (2016) Collagenase 1A2 (COL1A2) gene a/C polymorphism in relation to severity of dental fluorosis. Community Dent Oral Epidemiol 44:162–168
Lindahl K, Rubin CJ, Brandstrom H et al (2009) Heterozygosity for a coding SNP in COL1A2 confers a lower BMD and an increased stroke risk. Biochemi Biophys Res Commun 384:501–505
Ling Y, Gao X, Lin H et al (2015) A common polymorphism rs1800247 in osteocalcin gene was associated with serum osteocalcin levels, bone mineral density, and fracture: the Shanghai Changfeng study. Osteoporos Int 27:769–779
Ba Y, Huang H, Yang Y et al (2009) The association between osteocalcin gene polymorphism and dental fluorosis among children exposed to fluoride in People’s Republic of China. Ecotoxicol Environ Saf 72:2158–2161
Zhao H, Pfeiffer R, Gil MH (2003) Haplotype analysis in population genetics and association studies. Pharmacogenomics 4:171–178
Acknowledgments
The authors are thankful to all the subjects who participated in the study. Mr. Moizul Haq and Mr. Abdul Hannan from Rampurhat Paribesh Pariseva Kendra are duly acknowledged for their cooperation in questionnaire survey, enrollment of subjects, and sample collection. KRC, NEERI, is duly acknowledged for checking the manuscript through the anti-plagiarism software iThenticate (KRC No: CSIR-NEERI/KRC/2019/DEC/KZC/1 dated December 3, 2019).
Funding
This work was financially supported by a grant from the Department of Biotechnology, Government of India (Project No. BT/PR8283/MED/12/619/2013), to Dr. Sreemanta Pramanik.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The protocol of the research study was approved by the Institutional Ethics Committee of CSIR-National Environmental Engineering Research Institute (CSIR-NEERI), Nagpur, India.
Conflict of Interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOC 294 kb)
Rights and permissions
About this article
Cite this article
Saha, D., Goswami, R., Majumdar, K.K. et al. Evaluating the Association Between Dental Fluorosis and Polymorphisms in Bone Development and Mineralization Genes Among Population from a Fluoride Endemic Region of Eastern India. Biol Trace Elem Res 199, 1–8 (2021). https://doi.org/10.1007/s12011-020-02116-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-020-02116-9