| PurposeTo explore gene specific distribution of nine susceptible loci(rs3761959?rs1024161?rs4947296?rs6903608?rs6457617?rs2281388?rs9355610?rs12101261?rs6832151)of Graves' disease(GD)susceptibility genes in Shandong Linyi Han population,also to make sure whether the 9 loci are TAO susceptibility loci of Han population in this region.And to study the relationship between single nucleotide polymorphisms(SNPs)of susceptibility loci and serum thyroid stimulating hormone receptor antibody(TRAb)in patients with TAO.Methods1.A total of 90 patients with TAO who were first diagnosed in Linyi People's Hospital Department of Endocrinology in Shandong province were selected as the case group,including thirsty-six males and fifty-four females,with a mean age of(35.4 ± 13.1).At the same time,we choose the same region and no blood relationship of 100 cases from GD non TAO patients as control group,of which 40 cases of males,with an average age of(38.6 ±11.9)years old.TAO patients were chosen according to the 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy and the classification criteria of the American Thyroid Association(ATA),and on the basis of China 2008 the Guide on Diagnosis and Treatment of thyroid disease,we elected the population of the Graves' disease.Exclusion criteria for both groups were eliminated by internal tumor,inflammation and other causes of eye disease,other immunological diseases and smoking,anti-thyroid medication,radioactive iodine treatment other factors.2.The elbow vein blood was collected and stored at-80? refrigerator after centrifugation.Then the blood samples were transported to Shanghai Jiaotong University School of Medicine Affiliated Ruijin Hospital and the SNP genotyping were analyzed by TaqMan probe technique.3.Collect blood samples and thyrotropin receptor antibody(TRAb),free triiodothyronine(FT3),free thyroxine(FT4)and thyroid stimulating hormone(TSH)were measured to compare the case and control group.4.The Hardy-Weinberg balance of SNPs locus was examined by Haploview software.Results1.The single nucleotide polymorphisms of 2 loci of HLA gene and the loci of the FCRL3 gene were correlated with TAO.HLA rs4947296,rs2281388 SNPs and FCRL3 rs3761959 were associated with the TAO in the Han nationality of Linyi area,which the difference of FcRL3 allele rs3761959_A was the most significant(P=0.003,OR=1.86,95%CI:1.24-2.80).Besides between the correlation between HLA rs4947296,rs2281388 and thyoid-associated orbitopathy,respectively:rs4947296_C,P=0.035,OR=1.79,95%CI:1.04-3.09;rs2281388_C,P=0.048,OR=1.51,95%CI:1.00-2.27.2.There is an association between single nucleotide polymorphism of HLA gene rs2281388 and serum TRAb level in patients.HLA rs2281388 has three genotypes which include CC,TC and TT.The case group and control group were divided into two groups,respectively,with TRAb 6.3IU/L as the boundary.Logistic regression analysis found that CC,TC and TT three genotypes in the ratio differences constitute the two subgroups was statistically significant(P=0.003),and the high rate of TRAb of rs2281388_TT genotype were significantly higher than that of genotype rs2281388_CC(P=0.001,OR=8.00,95%CI:2.25-28.48),while above 6.3 IU/L rate of TRAb of rs2281388_TC genotype is higher than that of the rs2281388_CC genotype(P=0.011,OR=2.57,95%CI:1.24-5.34);at the same time using the RxC table Fisher accurate test statistics found that in the both case and control group of TT genotype were statistically significant difference between two subgroups(P=0.017,P=0.008),Allele T and high TRAb group also have certain relevance(P = 0.037,OR = 0.51,95%CI:0.27-0.96 and P =0.011,OR = 0.48,95%CI:0.28-0.85).3.HLA 2 gene loci rs4947296,rs2281388 and FcRL3 gene loci rs3761959 single nucleotide polymorphism with TAO patients clinical data such as gender,degree of goiter,age,FT3,FT4 and TSH level had no correlation(P>0.05).Conclusion1.HLA rs4947296,rs2281388 and FcRL3 rs3761959 may be associated with Linyi region Han TAO patients,among them with FcRL3 rs3761959_A relevance is strongest,might have a higher risk of the disease.2.HLA rs4947296,rs2281388 and FcRL3 rs3761959 single nucleotide polymorphisms were not associated with gender,thyroid diffused goiter,age,FT3,FT4,and TSH levels in patients with TAO disease.3.HLA rs2281388 single nucleotide polymorphisms was correlated with serum level of TRAb. |
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