| Objective To explore the association between the thyroid dysfunction and the six key genes( DIO1,IYD,TTF1,PAX8,PDE8 B,PTPN22) of the school-children from the Shandong province and understand the etiology and pathogenesis of the disease. Finally,it would provide the scientific evidence for the screening and preventing of thyroid diseases which are vulnerable to affect by some people.Methods We collected the blood clots and basic data of 500 thyroid dysfunction as case group and 500 normal individuals as control group from the iodine excess areas of the Shandong province. This study use the Sequenom Mass ARRAY technology to test the genotypes of 15 loci from the 6 key genes(DIO1, IYD, TTF1, PAX8, PDE8 B, PTPN22). Using case-control study design compared the genotype and allele frequency of the case group with the control group and analyze the association between the thyroid dysfunction and candidate gene loci. Using one-way analysis of variance to discuss the association between the genotypes of candidate gene loci and the levels of serum FT3, FT4, TSH.Results 1. The genotyping rates of all the candidate loci were more than 95%, conforming to the Hardy- Weinberg equilibrium, with P >0.05. 2.The results of a case-control study based on total groups show that the PAX8-rs4848323, PDE8B-rs4704397 and PDE8B-rs6885099 were significant with alleles and genotypes associated analysis. The significant SNP were PDE8B-rs4704397 and PDE8B-rs6885099 in the iodine excess group when 24h-UIE>200mg. The Logistic regression analysis showed PDE8B-rs6885099 was significant. The rs6885099 was found that the individuals with mutant-genotypes AA were lower risk in thyroid dysfunction than the ones with the wild-genotype GG, the partial regression coefficient was 0.532, OR=1.702(1.221-2.370). Results of the one-way analysis of variance showed that the serum FT3,TSH levels of the individuals with the mutation homozygous genotype AG of the rs4704397 was higher than the one with wild-genotype AA, P=0.021. 3.The results of a case-control study based on goiter showed that the DIO1-rs2294512,PAX8-rs4848323,PDE8B-rs4704397,PDE8B-rs6885099,PTPN22-rs1970559 were significant with alleles and genotypes associated analysis between the case and control groups. The significant SNP was PAX8-rs4848323 in the iodine excess group when 24h-UIE>200mg. The Logistic regression analysis showed the PAX8-rs4848323 and PDE8B-rs6885099 were significant, for the PAX8-rs4848323, the individuals with mutation homozygote genotype CC has a lower risk in goiter than the ones with wild genotype TT, the partial regression coefficent is 0.744, OR=2.104(0.715-6.925). For the PDE8B-rs6885099, the individuals with mutation homozygote genotype AA has a lower risk in goiter than the ones with wild genotype GG, the partial regression coefficent is 0.928, OR=2.530(1.574-4.066). Results of the one-way analysis of variance showed the serum TSH levels of the individuals with mutation genotype GG the rs4704397 were lower than the ones with wild genotype AA,P=0.033. 4.The results of a case-control study based on hormone levels showed that the PAX8-rs4848323 and TTF1-rs2076735 were significant with alleles and genotypes associated analysis between the case and control groups. There was no significant SNP with hierarchical analysis based on the 24h-UIE. The Logistic regression analysis showed there were no significant factors. Results of the one-way analysis of variance showed that the serum FT3, TSH levels of the individuals with the mutation homozygous genotype CC of the rs4848323 was higher than the one with wild-genotype TT, P=0.020, 0.024. 5.The results of a case-control study based on antibody levels showed that the PTPN22-rs1970559 was significant with alleles and genotypes associated analysis. There was no significant SNP with hierarchical analysis based on the 24h-UIE. The Logistic regression analysis showed there were no significant factors. Results of the one-way analysis of variance showed rs1970559 was associate with TSH, P=0.031.Conclusion 1.The study screened out 6 SNP loci which were associated with the susceptibility to thyroid dysfunction. TTF1-rs2076735 and PDE8B-rs4848323 were significant association with the abnormal hormone. PTPN22-rs1970559 was significant association with the abnormal antibodies. DIO1-rs2294512, PAX8-rs48483 23, PDE8B-rs4704397, PDE8B-rs6885099 and PTPN22-rs1970559 were significant association with goiter. 2.The results based on urinary iodine hierarchical analysis showed that DIO1-rs2294512, PDE8B-rs4704397 and rs6885099 were association with goiter with high iodine exposure. Futhermore, DIO1 and PDE8 B may have a influence in the process of goiter with higher iodine. |
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