Association between ESR1 and COL1A1 gene polymorphisms and skeletal fluorosis in Tibetan, Kazakh, Mongolian and Russian populations, China.

Background: Skeletal fluorosis is a chronic metabolic bone disease caused by excessive accumulation of fluoride in the bones. Previous studies have found that when the intake of tea fluoride is similar, the prevalence of skeletal fluorosis varies greatly among different ethnic groups, which may be related to different genetic backgrounds. Single nucleotide polymorphisms (SNPs) of estrogen receptor 1 (ESR1) and collagen type 1 α1 (COL1A1) were strongly associated with bone metabolism as well as bone growth and development, but their association with the risk of skeletal fluorosis has not been reported.

Purpose: To explore the incidence of skeletal fluorosis in different nationalities in the endemic fluorosis area of brick-tea type. To study the relationship between 4 SNPS of ESR1 and COL1A1 gene and skeletal fluorosis METHODS: A cross-sectional study was conducted in Inner Mongolia, Qinghai and Xinjiang. By including exclusion criteria, a total of 989 people were included in the study, demographic data were collected, and physical examinations and laboratory biochemical tests were performed. The X-ray of the participants were diagnosed according to the diagnostic criteria of Chinese endemic skeletal fluorosis (WS192-2008). Fluoride levels in tea or urine were measured using fluoride ion electrodes. SNP was evaluated using Sequenom-MassARRAY system.

Result: The prevalence of skeletal fluorosis varies among different nationalities. Binary logistic regression found that carried the ESR1 Rs9340799 G allele played a protective role in brick-tea-type fluorosis (OR=0.673[95% CI, 0.495,0.914]). Russians carried the COL1A1 Rs1800012 T allele had a significantly higher risk of developing skeletal fluorosis (OR=6.370 [95% CI, 1.413,28.715]). When stratified by sex, carriage of the T allele in COL1A1 Rs1800012 significantly increased the risk of developing skeletal fluorosis in Russian men. At the same time, changes in tea fluoride intake and older age can affect the effect of genetic background differences on the risk of skeletal fluorosis.

Conclusion: Our data suggested that there may be a genetic component to the risk of skeletal fluorosis in participants of different ethnicities and that this difference could modified by tea fluoride intake, sex or age.