| ObjectiveGraves disease is characterized by diffuse goiter and thyrotoxicosis and may be accompanied by an infiltrative orbitopathy and ophthalmopathy, and occasionally infiltrative dermopathy. It accounts for 80-85% of hyperthyroidisms. The concordance for Graves disease in monozygotic twins is 20-30%, compared to <5% in dizygotic twins. It suggests that gene is an important factor. Single nucleotide polymorphisms (SNPs) which account for over 90% genetic variations in human genome are the best genetic markers for explaining the hereditary susceptibility of diseases and suitable for quantitatively prediction. In this study, the selected susceptibility genes of GD were analyed to investigate the ralation of the SNPs and the Chinese syndrome, recurrence, the molecular mechanism of Fufangjiakang Tablets.MethodsThe data of susceptibility genes was established from the domestic and foreign literature database. The SNPs were selected by the etiology. Genomic DNA was extracted by using ralax gene blood DNA system. Primer extension method, micro-sequencing technology and Matrix assisted laser desorption ionisation time-of-flight mass spectrometry (Matrix Assisted Laser Desorption/ionisation Time of Flight Mass Spectrometry, MALDI-TOF MS) were used to get SNP genotyping. The experimental data was analysed by the binary or multiple logistic regression analysis and loglinear model. Results1, Eight SNPs (rs231775, rs1883832, rs1800629, rs1990760, rs2268458, rs2076740, rs2476601, rs1042714) which locate on different genes (CTLA4, CD40, TNF, IFIH1, TSHR, Tg, PTPN22, ADRB2) were obtained;2, In this study, polymorphisms was found on CTLA4 (rs231775), CD40 (rs1883832), TNF (rs1800629), IFIH1 (rsl990760), TSHR (rs2268458) except PTPN22 gene (rs2476601), Tg (rs2268458), ADRB2 (rs1042714) were excluded for the false positive results;3, One hundred and twenty patients were recruited, including 87 cases (72.50%) of the Chinese Syndrome of Deficiency of both Qi and Yin,18 cases (15.00%) of the Chinese Syndrome of Stagnant Fire in Liver,15 cases (12.50%) of others. Comparing the former groups, there was no significant difference on gender, but there was significant difference on age (t=2.09, P=0.04) which the average age of the Chinese Syndrome of Deficiency of both Qi and Yin is 35.66±13.79. years and the average age of the Chinese Syndrome of Stagnant Fire in Liver is 28.44±10.73 years. The Chinese Syndrome of Deficiency of both Qi and Yin was associated with GG genotype (OR=0.18,P=0.03) and G allele (OR=0.19,P=0.04) of CTLA4 (rs231775). The Chinese Syndrome of Stagnant Fire in Liver was associated with GG genotype (P=0.00) of TNF (rs1800629) and CC genotype (OR=8.36, P=0.04) of TSHR (rs2268458);4, Eighty seven cases of the Chinese Syndrome of Deficiency of both Qi and Yin were divided into two groups of cure and recurrence, there was no significant difference on gender, age and severity of grading. The result suggests that GG genotype (OR=3.46,P=0.02) of CTLA4 (rs231775) was associated with the relapse; 5, When put the GG genotype of CTLA4 (rs231775), drugs and the relapse conditions into loglinear model to analyse the relationship, there was no significant difference of them.Conclusion1, Genetic factors play an important role in the pathogenes of GD, but its genetic susceptibility may determined by many different genes;2, The susceptibility gene of GD is relate to the Chinese Syndrome. The GG genotype of TNF (rs1800629) and the CC genotype of TSHR (rs2268458) are associated with the Chinese Syndrome of Stagnant Fire in Liver, and the GG genotype and G allele of CTLA4 (rs231775) are associated with the Chinese Syndrome of Deficiency of both Qi and Yin;3, The Chinese Syndrome of Deficiency of both Qi and Yin Qi dominate the Chinese syndrome of the GD, so the method of replenishing Qi and nourishing Yin is the main treatment;4, The GG genotype of CTLA4 (rs231775) plays an important role in recurrence;... |