Association analysis of gene polymorphism of osteoprotegerin with coal-burning endemic fluorosis in Guizhou Province / 中华地方病学杂志

ABSTRACT

Objective:To investigate the relationship between gene polymorphism of osteoprotegerin (OPG) and coal-burning endemic fluorosis in Guizhou Province.Methods:In 2018 and 2019, a case-control study was conducted in Bijie City, a typical coal-burning endemic fluorosis area in Guizhou Province, and 260 cases of coal-burning endemic fluorosis patients were selected as case group. According to the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS 192-2008), the case group was divided into severe group (130 cases) and mild group (130 cases). At the same time, 130 cases without dental fluorosis and skeletal fluorosis symptoms were chosen as control group in Changshun County, a non-coal-burning endemic fluorosis area in Guizhou Province. Whole blood genomic DNA was extracted, and real-time fluorescence quantitative PCR with TaqMan-MGB probe was utilized to type the OPG gene rs2460985, rs2073618, rs6469804 and rs6993813 four single nucleotide polymorphism (SNP) loci of all samples, and genetic model analysis was performed to compare the frequency distribution of its alleles, genotypes and constructed haplotypes in control, mild and severe groups. Results:By Hardy-Weinberg equilibrium test, the genotype frequencies of the four SNP loci all reached genetic balance in control, mild and severe groups ( P > 0.05). There was a statistically significant difference in the genotype frequency of OPG gene rs6469804 locus among the three groups (χ 2 = 10.615, P < 0.05), and the difference in the genotype frequency of this locus between the control group and the severe group was statistically significant (χ 2 = 6.784, P < 0.05). The results of genetic model analysis showed that in comparison between the control group and the severe group, the optimal genetic model of rs6469804 locus was the overdominant genetic model, the frequency distribution of genotypes AA + GG and AG in the control group and the severe group was statistically significant [odds ratio ( OR) = 1.94, 95% confidence interval ( CI) 1.16 - 3.23, P < 0.05], genotype AG was a risk factor for coal-burning endemic fluorosis. In comparison between the control group and the mild group, the optimal genetic model of rs2073618 locus was the recessive genetic model, the frequency distribution of genotypes GG + GC and CC in the control group and the mild group was statistically significant ( OR = 3.17, 95% CI 1.08 - 9.30, P < 0.05), genotype CC was a risk factor for coal-burning endemic fluorosis. In comparison between the control group and the mild group, haplotypes C-C-G-T and T-G-A-C were risk factors for coal-burning endemic fluorosis (adjusted OR = 2.41, 1.98, 95% CI 1.29 - 4.50, 1.22 - 3.23, P < 0.05); in comparison between the control group and the severe group, haplotype T-G-A-C was a risk factor for coal-burning endemic fluorosis (adjusted OR = 1.87, 95% CI 1.14 - 3.07, P < 0.05). Conclusion:OPG gene rs6469804 locus genotype AG and rs2073618 locus genotype CC may be risk factors for coal-burning endemic fluorosis.