| Objective To investigate clinical features and immune function in autoimmune thyroid disease;to analyze and compare clinical features,family history and amynology indexes between GD group and HT group;to discussion the role of immune dysfunction on the pathogenesis of AITD. Methods 1005 subject(s303 control subjects and 702 AITD patients)were enrolled. According to the diagnosis criteria of internal medicine five-year teaching material (sixth edition),all subjects were divided into three groups as follow:normal contro(lNC group,303 subjects),patients with Graves'disease(GD group,584 patients)and patients with Hashimoto's thyroiditis(HT group,118 patients). For all subjects, thyroid gland size and ophthalmic signs were evaluated , TT3,TT4,FT3,FT4,uTSH,TRAb,TgAb and TPOAb were assayed.Results⑴There existed genetic predisposition in GD and HT, and the frequency of family history in GD group was higher than that of HT group(23.4% vs 14.4%,P<0.05).⑵Compared with HT patients,the age of onset was younger (P<0.05),the positive ratio of ophthalmic signs and goiter was higher in GD group(56.3% vs 24.8%,P<0.01;65.4% vs 25.0%,P<0.01,respectively).⑶TRAb,TgAb and TPOAb are objective indexes to appraise thyroid immune dysfunction. There did exist thyroid immune dysfunction in GD and HT patients. The positive ratio and antibody titer of TgAb and TPOAb in HT patients were both higher than that of GD patients.⑷. Compared with HT patients,FT3,FT4,TT4 in GD group increased,uTSH in GD group decreased,and the difference was significance(P<0.05).Conclusion There exist genetic predisposition in GD and HT patients, and the frequency of family history in GD group is higher than that of HT group. There exist thyroid immune dysfunction in GD and HT patients. Compared with GD group, the positive ratio and antibody titer of TgAb and TPOAb in HT group are both higher. The findings show that heredity and thyroid autoimmune dysfunction may have concerned with the pathogenesis of AITD. Objective To study the association of single nucleotide polymorphisms ( SNPs ) in FCRL3 gene with AITD, clinical characteristics and immunity indexes.Methods The DNA samples of 303 controls and 702 AITD patients(584 GD and 118 HT patients)were selected to identify SNPs in FCRL3 gene. Three SNPs in promoter, exon2 and exon4 of FCRL3 gene were screened by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) and DNA sequencing. Then pairwise linkage disequilibrium(LD)test and haplotype were examined. Three SNPs of FCRL3 were genotyped by case-control method in Chongqing area to investigate its genetic association with AITD.Results⑴There did exit single nucleotide polymorphisms in promoter, exon2 and exon4 of FcRL3 gene. LD analysis showed that D′values between promoter and exon2 was above 0.7. It suggested that the both SNPs were in a haplotype block.⑵Case-controls study on promoter, exon2 and exon4 of FcRL3 gene showed that the three SNPs of FcRL3 gene were associated with GD(P<0.05), and FcRL3 gene exon4 SNP were associated with HT(P<0.05).⑶There was significant difference in family history frequency in GD group with different genotypes in promoter of FcRL3 gen(eP<0.05), and no significant difference in age of onset,ophthalmic signs,goiter,TRAb,TgAb and TPOAb in GD group compared between three genotypes of others SNP(sP>0.05).⑷Between two LD SNPs genotyped, three common haplotypes accounted for 95.2% of the observed haplotypes. The frequency of haplotype H2 was higher in GD group than that in control group, and the frequency of haplotype H3 was higher in HT group than that in control group(50.8% vs 32.1%,p<0.01, 11.6% vs 4.2%,p<0.01, respectively).Conclusion FcRL3 gene promoter,exon2 and exon4 three SNPs and H2 haplotype are associated with GD, and FcRL3 gene exon4 SNP and H3 haplotype are associated with HT. FcRL3 gene SNPs are associated with GD and HT, and may contribute to genetic predisposition to AITD. Objective To study the association of single nucleotide polymorphism(SNP)in PTPN22 gene with AITD.Methods The DNA samples of 216 controls and 352 AITD patients(279 GD and 73 HT patients)were selected to identify SNP in PTPN22 gene. The A1858G SNP in exon14 of PTPN22 gene were screened by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) and DNA sequencing. PTPN22 gene A1858G SNP was genotyped by case-control method in Chongqing area to investigate its genetic association with AITD.Results⑴There was no AA genotype and a few A allele in 1858 site of PTPN22 gene in Han Chongqing area China. The A allele frequency was as well as that of Asia people, but much fewer than that of Caucasus.⑵There was no significant difference of the A allele frequency at 1858 site of PTPN22 in GD or HT patients compared with those of normal group(1.4% vs 1.2%,х2=0.137,p>0.05; 0.0% vs 1.1%,х2=2.903,p>0.05,respectively). After adjustment of age and sex,compared with normal group, the AG genotype frequency difference of PTPN22 gene in GD or HT patients was no significance (recessive model: OR=0.805,95%CI=0.256～2.533,p>0.05;OR=0.435,95%CI=0.184～1.031,p>0.05,respectively). Our data showed that the A/G single nucleotide polymorphisms was not associated with autoimmune thyroid disease(GD and HT).Conclusion There are a few A alleles in 1858 site of PTPN22 gene in Han Chongqing area. The 1858A allele of PTPN22 is not associated with GD or HT,it may not contribute to genetic predisposition to AITD. Objective To investigate the association of single nucleotide polymorphism(SNP)in FcγRⅡB gene with AITD. To discuss the effect of interactions between FcRL3,FcγRⅡB and PTPN22 genes on the risk of AITD(GD and HT).Methods Case-control analysis was studied to investigate genetic association of SNP in FcγRⅡB gene with AITD. The A/T variants in exon4 were genotyped in 206 controls and 655 AITD patients( 572 GD and 83 HT patients ) by PCR-RFLP and DNA sequencing. Multifactor dimensionality reduction(MDR) and logistic regression were used to analyze gene-gene interaction of FcRL3,FcγRⅡB and PTPN22 genes.Results⑴There was a very few TT genotypes and some T alleles in exon4 of FcγRⅡB gene in Han Chongqing area China.⑵There was no significant difference of the T allele frequency in exon4 of FcγRⅡB gene in GD or HT patients compared with those of normal group(11.7% vs 10.6%,х2=0.486,p>0.05;10.8% vs 10.6%,х2=0.002,p>0.05,respectively). After adjustment of age and sex,compared with normal group,the AT genotype frequencies difference of FcγRⅡB gene in GD or HT patients was also no significance (additive model: OR=0.852,95%CI=0.595～1.221,p>0.05;OR=0.924,95%CI=0.501～0.704,p >0.05,respectively). Our data showed that among patients with AITD, the T allele was not associated with autoimmune thyroid disease.⑶There was not interactions between FcγRⅡB and FcRL3 or PTPN22 gene to the development of AITD.⑷The interactions of five SNPs of FcRL3,FcγRⅡB and PTPN22 gene was not associated with GD, while the interactions of three SNPs of FcRL3(Promoter,exon2 and exon4) was associated with HT.Conclusion FcγRⅡB gene exon4 SNP is not associated with GD or HT in Han Chongqing area. it may be not correlation with genetic predisposition to AITD. There isn't interactions between FcγRⅡB and FcRL3 or PTPN22 gene to the development of AITD. The interactions between five SNPs of FcRL3,FcγRⅡB and PTPN22 gene is not associated with GD, while the interactions between three SNPs of FcRL3(Promoter,exon2 and exon4)is associated with HT.
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