Study On The Association Between Thyroid-hormone-Synthesis-related Gene Polymorphisms And Hypothyroidism

Objective To explore the the relationship between the candidate SNPs polymorphism of 5 key genes of thyroid hormone synthesis(SLC5A5,TSHR,TG,TPO,DUOX2)and the hypothyroidism susceptibility of Chinese han population(CHB).Analyses the correlations between the candidate SNPs polymorphism and the levels of serum FT3,FT4,TSH,finding the SNPs that influencing the thyroid functions.Methods We collected the general features,clinical results,laboratory examination results and blood samples of 347 hypothyroidism patients and 337 normal individuals as controls in optimal iodine regions.Screen for the tagSNPs of candidate genes based on the principle of Linkage Disequilibrium.Test the genotypes of 15 SNPs of SLC5A5,TSHR,TG,TPO and DUOX2 with Sequenom MassARRAY technology.Utilize the case-control study to comparethe rate differences of alleles and genotypes in patients with hypothyroidism and controls,to uncover the associations between the polymorphisms of candidate SNPs and the susceptibility of hypothyroidism.Utilize the covariance analysis and rank-sam test to discuss the relationship between the genotypes of candidate SNPs and the levels of serum FT3,FT4,TSH.Results 1.The Sequenom genotyping rates of the 15 SNPs were without exception more than 95%,and the P values all exceed 0.05,conforming to the Hardy Weinberg equilibrium.2.Results of the association analysis of allele showed that TG-rs2741202 and TG-rs3739266 were associated with the susceptibility of hypothyroidism,P values were 0.048 and 0.038 respectively.C allele of rs2741202 and T allele of rs3739266 can increase the risk of the morbidity of hypothyroidism.3.Results of the association analysis of genotypes showed that only TPO-rs1126799 and TG-rs2741202 were related to the susceptibility of hypothyroidism(P=0.067,P=0.098).4.Results of the genotypes of gender stratification analysis showed that there were strong correlations trend between the male TSHR-rs3783941,TPO-rs1126799,SLC5A5-rs11672428 and the risk of hypothyroidism for male,but the correlation is not significant(P=0.050,P=0.063,P=0.072).While there were no significant associations between candidate SNPs and the risk of hypothyroidism for female.5.Results of the logistic regression analysis showed that two statistically significant variables were selected:gender and TG-rs3739266.Odds Ratio of the gender factor is 0.247,suggesting that females are more susceptible to HT than males,onset risk is 4.049.Odds Ratio of the loci TG-rs3739266 is 1.372,suggesting that people carrying mutation genotype are more susceptible to HT than people carrying wild genotype.The partial regression coefficients in the regression model were-1.398 and-0.316,respectively.6.Results of the correlation analysis showed that TG-rs2741202 was correlated with the levels of serum FT3(P<0.05)before adjusted the influences of age and gender,while the significance just disappeared when adjusted the influences of age and gender.SLC5A5-rs11672428 correlated with the levels of serum FT4 before and after adjusted the influences of age and gender(P=0.004,P=0.003).And the levels of serum FT4 of individuals carrying the heterozygosis genotype CT were lower than the wild genotype TT carriers.TG-rs3739266 was correlated with the levels of serum TSH for all of the females.Conclusions 1.The polymorphism of TG-rs3739266 was associated with the susceptibility of hypothyroidism.Although there was no significant relationship between the polymorphism of TPO-rs1126799,TG-rs2741202,TG-2069568 and the susceptibility of hypothyroidism,there was strong correlation trend.2.There were potential association between the polymorphism of TSHR-rs3783941,TPO-rs1126799,SLC5A 5-rs 11672428 and the onset risk of hypothyroidism for males,though the correlations were not significant.The mutation allels of the former one locus was likely to reduce the risk of hypothyroidism,while the mutation allels of the latter two loci were likely to rise the risk of hypothyroidism.3.The polymorphism of TG-rs3739266,TG-rs2741202 and 5-rs 11672428 was associated with the serum levels of TSH?FT3?FT4,respectively.The mutation allel of TG-rs3739266 can rise the level of TSH.The mutation allel of TG-rs2741202 can reduce the level of FT3.The mutation allel of SLC5A5-rs11672428 can reduce the level of FT4.