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目的:探讨骨保护素（OPG）基因多态性与贵州省燃煤污染型地方性氟中毒（简称燃煤型地氟病）的关系。方法:2018、2019年，采用病例对照研究方法，在贵州省典型燃煤型地氟病病区毕节市选取燃煤型地氟病患者260例作为病例组，根据《地方性氟骨症诊断标准》（WS 192-2008）将病例组分为重症组和轻症组，每组130例；同时，在贵州省非燃煤型地氟病病区长顺县选取无氟斑牙及氟骨症症状者130例作为对照组。提取研究对象全血基因组DNA，采用n TaqMan-MGB探针实时荧光定量PCR法对所有样本OPG基因rs2460985、rs2073618、rs6469804、rs6993813 4个单核苷酸多态性（SNP）位点进行基因分型和遗传模式分析，比较其等位基因、基因型及所构建的单倍型在对照、轻症、重症组中频率分布的差异。n 结果:经Hardy-Weinberg平衡检验，4个SNP位点基因型频率在对照、轻症、重症组中均达到遗传平衡（n P均> 0.05）。OPG基因rs6469804位点基因型频率组间比较差异有统计学意义（χn 2 = 10.615，n P < 0.05），且该位点基因型频率对照组与重症组比较差异有统计学意义（χ n 2 = 6.784，n P < 0.05）。遗传模式分析结果显示，rs6469804位点对照组与重症组比较最优遗传模式为超显性遗传模式，在该模式下基因型AA + GG和AG频率分布差异有统计学意义[比值比（ n OR）= 1.94，95%置信区间（n CI）：1.16 ~ 3.23，n P < 0.05]，基因型AG是燃煤型地氟病发生的危险因素；rs2073618位点对照组与轻症组比较最优遗传模式为隐性遗传模式，在该模式下基因型GG + GC和CC频率分布差异有统计学意义（ n OR = 3.17，95%n CI：1.08 ~ 9.30，n P < 0.05），基因型CC是燃煤型地氟病发生的危险因素。对照组与轻症组比较，单倍型C-C-G-T、T-G-A-C是燃煤型地氟病发生的危险因素（调整 n OR = 2.41、1.98，95%n CI：1.29 ~ 4.50、1.22 ~ 3.23，n P均< 0.05）；对照组与重症组比较，单倍型T-G-A-C是燃煤型地氟病发生的危险因素（调整n OR = 1.87，95%n CI：1.14 ~ 3.07，n P 0.05). There was a statistically significant difference in the genotype frequency of OPG gene rs6469804 locus among the three groups (χ n 2 = 10.615, n 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 n 2 = 6.784, n 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 ( n OR) = 1.94, 95% confidence interval (n CI): 1.16 - 3.23, n 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 ( n OR = 3.17, 95%n CI: 1.08 - 9.30, n 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 n OR = 2.41, 1.98, 95%n CI: 1.29 - 4.50, 1.22 - 3.23, n 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 n OR = 1.87, 95%n CI: 1.14 - 3.07, n P < 0.05).n Conclusion:OPG gene rs6469804 locus genotype AG and rs2073618 locus genotype CC may be risk factors for coal-burning endemic fluorosis.