ABSTRACT
OBJECTIVE: To evaluate the variables which can be used as prognostic factors in predicting the outcome of Graves disease (GD) after treatment with antithyroid drugs. METHODS: We performed a retrospective audit of 204 patients with newly diagnosed Graves disease consecutively at the Ruijin Hospital. RESULTS: Overall, 110 patients (53.9%) were considered to be treatment failures. Age at the time of diagnosis was (31.0 +/- 12.2)years in the successful group and (36.3 +/- 14.0) years in the failure group. Free T3 (FT3) was (25.60 +/- 9.52) pmol/L and (19.16 +/- 6.38) pmol/L in the failure and the successful group (P = 0.001). FT3 to FT4 ratio and thyrotrophin receptor antibody (TRAb) levels were higher in the failure group (P = 0.001). Logistic regression analysis showed that thyroid size, FT3 to FT4 ratio and TRAb at the time of diagnosis were associated with failure outcome. The patients reached euthyroid state at 3, 6, 9 and 12 months respectively and in the failure group the patients with continued thyrotropin suppression were more than those in the successful group (P = 0.001). CONCLUSIONS: Graves disease patients with large thyroid size, high levels of TRAb and FT3 to FT4 ratio before drug treatment are more likely to fail to respond to antithyroid drug treatment. We also found that patients with continuing thyrotropin suppression and attainment of euthyroid state in the course of treatment had low remission rate and prolonged therapy.
Subject(s)
Antithyroid Agents/therapeutic use , Graves Disease/drug therapy , Adolescent , Adult , Aged , Female , Follow-Up Studies , Graves Disease/immunology , Graves Disease/metabolism , Humans , Immunoglobulins, Thyroid-Stimulating/metabolism , Logistic Models , Male , Middle Aged , Prognosis , Receptors, Thyrotropin/immunology , Recurrence , Retrospective Studies , Thyroxine/metabolism , Triiodothyronine/metabolism , Young AdultABSTRACT
Interleukin (IL)-16 was one of the cytokines with the function of T helper cell recruitment, whose expression in the thyrocyte and orbital fibroblast of Graves' disease (GD) patients was increased. Recently association of IL-16 gene polymorphisms with autoimmune diseases had been reported. However, there was little known about the impact of IL-16 gene polymorphisms on GD. In this study, we performed a case-control association study of three tagSNPs (rs4778889-rs1131445-rs4778641) within the IL-16 gene on 258 patients with GD and 208 healthy subjects in the Chinese population. Our data showed that common IL-16 variants were associated with GD (P=0.013-0.0186) and Graves' disease associated ophthalmopathy (GO) (P=0.0033-0.041). A novel protective haplotype containing the three tagSNPs (C-T-C) was observed in association with GO (P=0.013). In conclusion, IL-16 gene was significantly associated with susceptibility to Graves' disease and Graves' disease associated ophthalmopathy in the Chinese population.
Subject(s)
Genetic Predisposition to Disease , Graves Disease/genetics , Interleukin-16/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Aged , Alleles , Child , China , Female , Genotype , Graves Disease/immunology , Humans , Interleukin-16/immunology , Male , Middle AgedABSTRACT
Genetic susceptibility plays a major role in the etiology of Graves' disease (GD). A recent study revealed that the A946T polymorphism (rs1990760) in interferon induced helicase (IFIH1) gene was a susceptible locus for GD. A case-control study in a Chinese population was undertaken, with 261 GD patients and 206 healthy subjects, to analyze the association of A946T polymorphism in IFIH1 gene with GD. In addition, the distribution of IFIH1 genotypes was investigated in subgroups according to the onset age and the Graves' ophthalmopathy (GO). No significant differences in the allele and genotype frequencies for A946T polymorphism were found between GD patients and healthy controls (chi2 = 2.834, P = 0.242; chi2 = 1.127, P = 0.288). The genotype-phenotype correlation was not identified either. Therefore we were unable to find the association of A946T polymorphism of the IFIH1 gene with the development of GD in a Chinese population.
Subject(s)
Asian People/genetics , DEAD-box RNA Helicases/genetics , Genetic Predisposition to Disease/genetics , Graves Disease/genetics , Polymorphism, Single Nucleotide/genetics , Adolescent , Adult , Age of Onset , Aged , Asian People/ethnology , Case-Control Studies , Child , China , Female , Gene Frequency , Genetic Predisposition to Disease/ethnology , Genotype , Graves Disease/ethnology , Graves Ophthalmopathy/ethnology , Graves Ophthalmopathy/genetics , Humans , Interferon-Induced Helicase, IFIH1 , Male , Middle AgedABSTRACT
OBJECTIVE: In order to study the association of G241R polymorphism of ICAM-1 gene with an earlier onset of Graves' disease (GD) and the susceptibility of K469E polymorphism to Graves' ophthalmopathy (GO) in Chinese population. STUDY DESIGN: A case-control and replication study was performed in 212 GD patients and 204 healthy subjects to analyze the genotypes. Furthermore the distribution of ICAM-1 genotypes was investigated in subgroups of patients with GD according to the onset age and the ophthalmopathy. RESULTS: No G241R polymorphism of ICAM-1 gene was detected in Chinese. No significant differences of allele and genotype frequencies regarding K469E polymorphism were found between GD patients and healthy controls (chi2 = 0.092, P = 0.762; chi2 = 1.089, P = 0.580). In addition, the genotype-phenotype correlation was not identified either. CONCLUSIONS: We found no association of G241R and K469E polymorphisms of the ICAM-1gene with the development of GD in a Chinese population. However, we could not rule out possible contributions of other polymorphisms of the ICAM-1gene to the pathogenesis of GD. Therefore, further studies are needed to elucidate the role of ICAM-1gene in Graves' disease in different population.
Subject(s)
Graves Disease/genetics , Intercellular Adhesion Molecule-1/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Aged , Aged, 80 and over , Child , China , Female , Gene Frequency , Genotype , Humans , Male , Middle AgedABSTRACT
OBJECTIVE: Graves' disease (GD) is an autoimmune disorder with genetic predisposition. There is strong evidence that members of the selectin family participate in the interaction between leucocytes and the endothelium, as well as in inflammatory cell recruitment. Moreover, a high serum level of a soluble form of L-selectin (SL-selectin) has been reported in untreated GD patients. However, the impact of L-selectin polymorphisms on GD has not yet been investigated. The aim of the present study was to elucidate whether L-selectin gene polymorphisms were associated with the development of GD. SUBJECTS AND DESIGN: L-selectin gene polymorphisms were investigated in 230 Chinese GD patients and 208 healthy control subjects without antithyroid autoantibodies or a family history of autoimmune disorders. Two L-selectin SNPs were genotyped by the PCR-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: A C/T polymorphism at position -642 of the promoter region and a Pro213Ser (c.725 C-T) polymorphism in exon 6 were examined using PCR-RFLP. There was a significant increase in -642T allele frequency in GD patients compared with healthy controls (70 vs. 62%; P = 0.0126; P(c) = 0.0252). The frequency of the c.725C allele in exon 6 also appeared higher in GD patients than in controls. Haplotype analysis showed a significant decrease in the -642C/c.725T haplotype in GD patients (26 vs. 34%; P = 0.0095; Pc = 0.0190). However there was no association between polymorphisms and certain GD clinical phenotypes, including age of onset and ophthalmopathy. CONCLUSIONS: L-selectin gene polymorphisms are associated with GD susceptibility in Chinese patients.
