No abstract available.
Genetics* ; Graves Disease*

The polymorphisms of thyroid stimulating hormone receptor (TSHR) intron 1 rs179247 and rs12101255 have been found to be associated with Graves' disease (GD) in genetic studies. In the present study, we conducted a meta-analysis to examine this association. Two reviewers systematically searched eligible studies in PubMed, Web of Science, Embase and China Biomedical Literature Database (CBM). A meta-analysis on the association between GD and TSHR intron 1 rs179247 or rs12101255 was performed. The odd ratios (OR) were estimated with 95% confidence interval (CI). Meta package in R was used for the analyses. Seven articles (13 studies) published between 2009 and 2014, involving 5754 GD patients and 5768 controls, were analyzed. The polymorphism of rs179247 was found to be associated with an increased GD risk in the allele analysis (A vs. G: OR=1.40, 95% CI=1.33-1.48) and all genetic models (AA vs. GG: OR=1.94, 95% CI=1.73-2.19; AA+AG vs. GG: OR=1.57, 95% CI=1.41-1.74; AA vs. AG+GG: OR=1.54, 95% CI=1.43-1.66). The site rs12101255 also conferred a risk of GD in the allele analysis (T vs. C: OR=1.50, 95% CI=1.40-1.60) and all genetic models (TT vs. CC: OR=2.22, 95% CI=1.92-2.57; TT+TC vs. CC: OR=1.66, 95% CI=1.50-1.83; TT vs. TC+CC: OR=1.74, 95% CI=1.53-1.98). Analysis of the relationship between rs179247 and Graves' ophthalmopathy (GO) showed no statistically significant correlation (A vs. G: OR=1.02, 95% CI=0.97-1.07). Publication bias was not significant. In conclusion, GD is associated with polymorphisms of TSHR intron 1 rs179247 and rs12101255. There is no association between rs179247 SNPs and GO.
China ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Graves Disease ; genetics ; pathology ; Graves Ophthalmopathy ; genetics ; pathology ; Humans ; Introns ; genetics ; Male ; Polymorphism, Single Nucleotide ; Receptors, Thyrotropin ; genetics ; Risk Factors

This study was conducted to screen the endocrine exophthalmos-associated genes or cDNA fragments and provide a basis for exploring the pathogenesis. The cDNA from the thyroid tissues of patients with hyperthyroidism and endocrine exophthalmos (HT&EE) was used as tester cDNA, and that from the thyroid tissues of patients with HT but free from EE was used as driver cDNA. The subtractive PCR products between tester and driver cDNA were obtained through two cycles of subtraction hybridization and two cycles of PCR by using suppression subtractive hybridization, and then were inserted into pT-Adv, a cloning vector. The ligated DNAs were transformed into E. coli DH5alpha competent cells and incubated for proper blue/white color development. Forty-eight white colonies were randomly picked and their inserts were colony PCR amplified. The PCR product from one of the colonies contained two inserts; the others contained single insert, having a size of 0.2 kb to 2 kb. The inserts of transformants were arrayed on nylon membrane. After cDNA/Rsa I digestion the thyroid tissues of patients with HT, and of patients with HT&EE, were labeled with digoxigenin; the nylon membranes were then hybridized respectively with the two cDNA probes for a high throughput screening for positive clones. The clones which were hybridized with the cDNA probe of HE&EE patients but not hybridized with the probe of the HT patients or showed only faint signal of hybridization, were chosen as positive clones and their inserts were candidates for the endocrine exophthalmos genes or cDNA fragments. About 50% of the clones were confirmed as positive clones. The cDNA fragments in the positive clones were the endocrine exophthalmos-associated genes or cDNA fragments. Endocrine exophthalmos
Cloning, Molecular ; DNA, Complementary ; genetics ; Graves Disease ; genetics ; Humans ; Polymerase Chain Reaction

OBJECTIVETo compare the efficacy of different expression vectors, target genes, and immunization procedures in transfecting mice via liposome to construct murine model of Graves disease.

METHODSWe linked pCDNA3.1(+) and pUBC to full-length human TSHR and TSHR A subunit cDNA to yield four plasmids, which were later injected intramascularly or subcutaneously into female Balb/c mice via liposome. The blood anti-TSHR antibody (TRAb) were determined and the body weight were measured after each immunization. Serum thyroid hormone levels were measured after the animals were sacrificed.

RESULTSIn mice immunized with pUBC, no significant variance with control in weight nor serum TRAb concentration was observed. Weight gain in pCDNA3.1(+) group was significantlyly slower than controls (p<0.05), and serum TRAb concentration was also significantly elevated. In pCDNA group, animals immunized with TSHR A subunit (TSHRA subgroup) as the target gene revealed even significantly slower weight gain (p<0.001) and even faster TRAb elevation than those immunized with full length TSHR. Significantly higher FT4 (p=0.023) was observed in TSHRA and TSHR subgroups, which was reversely correlated to weight gain, but no significant difference (p>0.05) in FT3 was observed. Weight gain and TRAb concentration mainly varied in the later period of immunization.

CONCLUSIONSImmunization with pCDNA3.1(+) and TSHR A subunit gene together with higher immunization frequency increases the chance of model induction. Furthermore, FT4 is a better indicator for assessing the thyroid function in this model.

Animals ; Disease Models, Animal ; Female ; Graves Disease ; genetics ; Liposomes ; Mice ; Mice, Inbred BALB C ; Receptors, Thyrotropin ; genetics ; Transfection

Human Sodium/Iodide symporter gene cDNA was amplified from thyroid tissue of the patient suffering from Graves disease by RT-PCR, and T/A cloned into pGEM-TEasy-NIS for sequencing, subcloned into shuttle plasmid pAdTrack-CMV which contained a green fluorescent protein (GFP) gene, and then forwarded to homologous recombinant in the bacteria BJ5183 that already contained AdEasy-1 plasmid. Positive recombinant adenovirus vector was selected, packaged and amplified in the 293 cells to obtain recombinant adenovirus. The results showed that the recombinant AdNIS was correctly constructed and confirmed by restriction enzyme analysis and PCR. The viral titer was 2. 5 - 3 x 10(9) efu/ml. So, the recombinant adenovirus vector carrying hNIS was successfully constructed, thus providing a basis for researches on 131I therapy in nonthyroid carcinoma.
Adenoviridae ; genetics ; metabolism ; DNA, Complementary ; genetics ; Genetic Vectors ; genetics ; metabolism ; Graves Disease ; genetics ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Symporters ; biosynthesis ; genetics

OBJECTIVETo investigate the association of Graves' disease and Graves' ophthalmopathy with the C/T transition polymorphism at position -318 of promoter and the A/G transition polymorphism at position 49 of exon 1 within cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene.

METHODSThirty-three patients with ophthalmopathy of Graves' disease, fifty-six Graves' patients without ophthalmopathy and sixty normal subjects as control were involved in the present case-control study. The polymorphisms were evaluated by polymerase chain reaction fragment length polymorphism (PCR-RFLP). Comparisons were made of gene frequencies and allele frequencies between the groups.

RESULTSThe gene frequencies of CT and allele frequencies of T were much higher in Graves' patients with ophthalmopathy than that in the group without ophthalmopathy (P=0.020, P=0.019). The gene frequencies of GG and allele frequencies of G in patients with Graves' disease were significantly increased as compared with control group (P=0.008, P=0.007). The data suggest that smokers with Graves' disease seemed to be more predisposed to ophthalmopathy than non-smokers (P=0.018).

CONCLUSIONOur results suggest that an allele of T at position -318 of promoter is associated with genetic susceptibility to Graves' ophthalmopathy while an allele of G at position 49 of exon 1 is associated with genetic susceptibility to Graves' disease instead. Smoking is believed to be a major risk factor for ophthalmopathy.

Adult ; Antigens, CD ; genetics ; Antigens, Differentiation ; genetics ; CTLA-4 Antigen ; Exons ; Female ; Genetic Predisposition to Disease ; Genotype ; Graves Disease ; complications ; genetics ; Graves Ophthalmopathy ; complications ; genetics ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Sensitivity and Specificity

Klinefelter's syndrome is one of the most common forms of primary hypogonadism and infertility in males. It is characterized by small and firm testes, gynecomastia, azoospermia, and an elevated gonadotropin level. The frequencies of diabetes mellitus, breast cancer, and germ cell neoplasia increases in Klinefelter's syndrome. We report upon a 35 year-old male patient with Graves' disease in association with Klinefelter's syndrome; as confirmed by chromosome analysis. The patient is being treated with antithyroid medication for Graves' disease and by testosterone replacement for Klinefelter's syndrome.
Adult ; Graves' Disease/*etiology/radionuclide imaging ; Human ; Hypogonadism/*etiology/genetics/pathology ; Klinefelter Syndrome/*complications/genetics/pathology ; Male

A 24-year-old Chinese woman with Graves' disease presented with myositis two months after treatment with carbimazole. The patient's myositis resolved with hydration and cessation of carbimazole. No other causes of myositis were found, and a change in the medication to propylthiouracil was uneventful. Review of the literature suggests a possible genetic susceptibility, as the majority of reported cases are Asian in origin, similar to patients who present with thyroid periodic paralysis. Changing the antithyroid drugs (ATDs) administered, decreasing the dose of pre-existing ATDs in the treatment regimen or addition of levothyroxine has been shown to result in clinical improvement of this complication. These observations suggest various mechanisms of carbimazole-induced myositis in the treatment of Graves' disease, including the direct effect of ATDs on myocytes, immune-related responses secondary to ATDs and rapid decrements in thyroid hormone with ensuing myositis.
Antithyroid Agents ; adverse effects ; Carbimazole ; adverse effects ; Female ; Genetic Predisposition to Disease ; Graves Disease ; drug therapy ; Humans ; Myositis ; chemically induced ; genetics ; therapy ; Young Adult

OBJECTIVE: To report the clinical and genetic characteristics of a rare case of Gitelman syndrome with comorbid Graves disease and ACTH-independent adrenocortical adenoma. METHODS: A patient who had presented at the Nanchong Central Hospital on December 21, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole-exome sequencing was carried out on DNA extracted from peripheral venous blood samples from the patient and her family members. RESULTS: The patient, a 45-year-old woman, was found to have Graves disease, ACTH-independent Cushing syndrome, hypokalemia and hypomagnesemia following the discovery of an adrenal incidentaloma. MRI scan had revealed a 3.8 cm × 3.2 cm mass in the left adrenal gland. The mass was removed by surgery and confirmed as adrenocortical adenoma. DNA sequencing revealed that the patient and her sister have both harbored compound heterozygous variants of the SLC12A3 gene, namely c.1444-10(IVS11)G>A and c.179(exon1)C>T (p.T60M), which were respectively inherited from their father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1444-10(IVS11)G>A and c.179(exon1)C>T (p.T60M) were respectively classified as a variant of uncertain significance (PM2_Supporting+PP3) and a likely pathogenic variant (PM3_Strong+PM1+PP3). CONCLUSION The conjunction of Gitelman syndrome with Graves disease and adrenal cortex adenoma is rather rare. The newly discovered c.1444-10(IVS11)G>A variant of the SLC12A3 gene, together with the heterozygous variant of c.179(exon1)C>T (p.T60M), probably underlay the pathogenesis in this patient.
Humans ; Female ; Middle Aged ; Gitelman Syndrome/genetics* ; Adrenocortical Adenoma ; Hypokalemia ; Graves Disease/genetics* ; Mothers ; Mutation ; Solute Carrier Family 12, Member 3

OBJECTIVETo investigate the relationship between CYP27B1 gene promoter polymorphism and autoimmune thyroid diseases.

METHODSA case-control study including 158 patients with Graves' disease (GD), 174 patients with Hashimoto's thyroiditis (HT) and 172 matched controls was conducted. Three genotypes of CYP27 B1 gene -1260 site (CC, AA and AC) were determined by restriction fragment length polymorphism (PCR-RFLP) assay and confirmed by sequencing.

RESULTSThe genotypic distribution of CYP27 B1 gene-1260 site showed no deviation from Hardy-Weinberg equilibrium. The genotype and allele frequencies of -1260A/C were CC34.3%, AA19.2%, AC46.5%, C57.6%, and A42.4% in the control group, 48.1%, 13.3%, 38.6%, 67.4%, and 32.6% in GD group, and 47.1%, 10.3%, 42.5%, 68.4%, and 31.6% in HT group, respectively. Significant difference was found in the genotype and allele frequencies in -1260A/C polymorphism between GD and the control groups (Chi2=6.80, P<0.05 for genotype frequencies, and Chi2=6.79, P<0.05 for allele frequencies) and between HT and the control groups (Chi2=8.39, P<0.05 for genotype frequencies, and Chi2=8.71, P<0.05 for allele frequencies).

CONCLUSIONCYP27 B1 promoter -1260 polymorphism is associated with GD or HT in Chinese Han population.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase ; genetics ; Adolescent ; Alleles ; Child ; Female ; Gene Frequency ; Genotype ; Graves Disease ; genetics ; Hashimoto Disease ; genetics ; Humans ; Linkage Disequilibrium ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Promoter Regions, Genetic ; genetics ; Thyroiditis, Autoimmune ; genetics