Association Of TSHR Gene Intron 1 And 4p14 Single-nucleotide Polymorphisms And Gene-gene Interactions With The Graves’ Disease

ObjectiveTo identify the association of thyroid stimulating hormone receptor（TSHR）gene intron 1 susceptible loci and 4P14 susceptible locus rs6832151 polymorphisms and Graves’disease（GD）in Han Chinese population in Bengbu,Anhui,China.To investigate the gene-gene interaction among TSHR intron 1 susceptible loci and 4P14susceptible locus rs6832151.These studies are to further reveal the pathogenesis of Graves.MethodsThe diagnosis of 611 cases in the case group was in accordance with the diagnostic criteria of GD in 2008,"China’s guidelines for the diagnosis and treatment of thyroid disease".There are 555 cases in the control group.The healthy people who are within three generations without kinship,over 40 years old（to exclude patients with late onset autoimmune disease）and and have gender matching meet our needs for the control group.We should collect Peripheral blood and extract DNA from it.Taqman fluorescent probes were used to genotype the SNP loci of TSHR intron 1 and rs6832151 loci.The serum indexes of GD patients（FT3,FT4,TSH,TRAb）were measured.We should make linkage analysis,correlation analysis,haplotype analysis and epistasis analysis with them by PLINK 1.07 software,SPSS17.0 software,Haploview 4.2 software,GMDR0.9 software.When p was less than 0.05,the results were statistically significantResults1.Six SNPs in two candidate genes（rs12101261,rs4903964,rs179247,rs2284722and rs17111394 in TSHR,rs6832151 in 4p14）were associated with GD.（P values are less than 0.05）2.The frequency distribution of haplotypes of SNPs in TSHR intron 1（AG TA,GGCG,AATA and CC）was statistically significant different between the GD patients and controls(X²=7.705,P=0.006;X²=36.002,P=1.971×10^-9;X²=16.019,P=6.270×10^-5;X²=7.368,P=0.007).3.The interaction between rs179247（TSHR）and rs12101261（TSHR）exist（P=0.001）;The interaction between rs179247（TSHR）,rs4903964（TSHR）and rs6832151（4p14）exist（P=0.001）.Conclusions1.rs683215 in 14p14 and rs12101261,rs4903964,rs179247,rs2284722 and rs17111394 in TSHR intron 1 were susceptible loci of GD in the Chinese Han population from Bengbu city.The haplotypes in TSHR intron 1 were associated with GD.2.The interaction between the SNPs in TSHR and 4p14 exist,which change the risk of GD.