RANK基因2个SNP位点多态性与贵州燃煤污染型地氟病患病风险的相关性

Correlation between 2 SNP loci of RANK gene polymorphism and morbid risk of coal-burning type of endemic fluorosis in Guizhou

目的探讨核因子κB受体活化因子(RANK)基因rsrs1505034、rs884205单核苷酸多态性(SNP)与贵州燃煤型地氟病患病风险的关系。方法483例贵州地氟病区人群按照氟斑牙诊断标准(WS/T 208-2011)分为地氟组(283例,氟斑牙程度在极轻度及以上)和对照组(200例,氟斑牙分度正常),采用TaqMan-MGB探针法对2组人群外周血DNA样本RANK基因的rs1505034、rs884205位点进行基因分型,分析rs1505034、rs884205等位基因和基因型在两组的分布,采用SNPstats对SNP位点基因型与燃煤型地氟病发生发展的相关遗传模式进行分析,采用SHEsis对RANK基因rs1805034和rs884205位点之间进行连锁不平衡分析。结果RANK基因rs1805034位点等位基因和基因型频率在地氟组和对照组比较,差异有统计学意义(P<0.05);最优遗传模式分析显示,RANK基因rs1805034位点最优遗传模式为共显性,在该遗传模式下C/T基因型和T/T基因型相对于C/C基因型是燃煤型地氟病发生的保护因素(OR=0.17,95%CI为0.09~0.31;OR=0.04,95%CI为0.02~0.08);rs884205位点与燃煤型地氟病的发生无相关性(P>0.05);SHEsis分析结果显示上述2个位点之间不存在连锁不平衡(D′<0.5)。结论RANK基因rs1805034位点多态型可能与贵州燃煤型地氟病的发生相关。

Objective To investigate the relationship between single nucleotide polymorphism(SNP)rsrs1505034 and rs884205 of Receptor Activator of Nuclear Factor-κB(RANK)gene and coal burning type of endemic fluorosis in Guizhou.Methods A total of 483 people were selected from endemic fluorosis area in Guizhou province.According to the diagnostic criteria for dental fluorosis(WS/T 208-2011),283 patients with extremely mild dental fluorosis and above were grouped as the fluorosis group,and 200 patients with normal dental fluorosis division were grouped as control group.The SNP loci rs1505034 and rs884205 of RANK gene in the above samples were genotyped by Taqman-MGB probe genotyping method,and the distribution differences of alleles rs1505034 and rs884205 in both groups were analyzed.SNPstats was adopted for analyzing relevant genetic models between SNP loci genotypeand coal-burning type of endemic fluorosis;SHEsis was adopted to analyze linkage disequilibrium between rs1505034 and rs884205 of RANK gene.Results The allele and genotype frequency of rs1805034 of RANK gene were statistically significantly different between the fluorosis group and the control group(P<0.05).The optimal genetic pattern analysis showed that rs1805034 of RANK gene as codominance;the C/T and T/T genotypes of such genetic model were associated with the risk of coal burning type of endemic fluorosis to C/C genotype(OR=0.17,95%CI was 0.09-0.31,P<0.001;OR=0.04,95%CI was 0.02-0.08,P<0.001).rs884205 loci showed no relevance with occurrence of coal burning type of endemic fluorosis(P>0.05).SHEsis analysis indicated that there is linkage disequilibrium in RANK gene polymorphism loci(D′<0.5).Conclusion The polymorphism of rs1805034 of RANK gene may be associated with the occurrence of coal-burning type of endemic fluorosis in Guizhou province.