Calcium and Phosphorus Levels in Saliva are Influenced by Genetic Polymorphisms in Estrogen Receptor Alpha and Microrna17.

Junia Ramos,Paulo Nelson-Filho,Paula Porto Spada,João Armando Brancher,Alexandre Rezende Vieira,Arthur S Cunha,Raquel Fernanda Gerlach,Lucas A Ramazzotto,Paula Cristina Trevilatto,Giovana Daniela Pecharki,Fernando Barbosa Jr,Erika Calvano Küchler

doi:10.1590/0103-6440202002934

Abstract

Homeostasis between salivary calcium and phosphorus is important for maintaining oral health. The aim of this study was to evaluate if polymorphisms in ESR1 (Estrogen Receptor Alpha), ESR2 (Estrogen Receptor Beta) and miRNA17 (microRNA17) are associated with calcium and phosphorus levels in saliva. Saliva from 276 12-year-old children were collected by masticatory stimulation and calcium and phosphorus levels were determined by Mass Spectrometry. Genomic DNA was extracted from remaining saliva and genetic polymorphisms in ESR1 (rs12154178, rs1884051, rs9340799 and rs2234693), in ESR2 (rs4986938 and rs1256049) and in miRNA17 (rs4284505) were genotyped using TaqMan chemistry and a real-time PCR equipment. Statistical differences in genotype and allele distributions between 'low' and 'high' calcium and phosphorus levels were determined using chi-square or Fisher´s exact tests. The analysis was also adjusted by sex (alpha of 5%). ESR1 rs9340799 had the less common genotype associated with higher calcium levels (p=0.03). The less common allele of ESR1 rs1884051 was associated with lower phosphorus levels (p=0.005) and there was an excess of heterozygotes for miRNA17 rs4284505 among individuals with lower calcium levels (p=0.002), both adjusted by sex. This study provides evidence that genetic polymorphisms in ESR1 and miRNA17 are involved in determining salivary calcium and phosphorus levels.

Highlights

The relationship between calcium and phosphorus levels with estrogen is not a new concept and has been widely explored
For the genetic polymorphism rs9340799 in ESR1, the genotypes distributions between “Low” and “High” calcium levels were statistically significant associated in the both analysis, additive model and additive model adjusted by the gender (p=0.03 and p=0.005, respectively)
For the genetic polymorphism rs4284505 in miRNA17 the genotypes distributions between “Low” and “High” calcium levels were statistically significant associated in the both analysis, additive model and additive model adjusted by the gender (p=0.01 and p=0.002, respectively)

Summary

Introduction

The relationship between calcium and phosphorus levels with estrogen is not a new concept and has been widely explored. Estrogen is one of the most widely known and discussed hormones. Estrogens play key roles in both male and female development, exerting a vast range of biological effects [1] including important effects on calcium and phosphorus homeostasis [2]. A negative whole-body calcium balance results from the lack of estrogen, which causes reduced calcium absorption in the gut and increased calcium excretion in the urine [3,4]. Studies on the effect that hormone replacement therapy exerts on oral environment of menopausal women proposed that estrogen might have a biological role in the oral environment [5,6]

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