Analysis of Immune Regulatory Genes' Copy Number Variants in Graves' Disease

Huber, Amanda K.; Concepcion, Erlinda; Gandhi, Alisha; Menconi, Francesca; Smith, Eric P.; Keddache, Mehdi; Tomer, Yaron

doi:10.1089/thy.2010.0262

Cited by 12 publications

(13 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, these results have potential implications for studies of CNV in complex diseases. It is now clear that immortalizing cell lines with EBV creates artificial CNVs and therefore, CNV analysis should only be done on DNA obtained from blood (20). …”

Section: Genetics and Aitdmentioning

confidence: 99%

Cutting Edge: The Etiology of Autoimmune Thyroid Diseases

Eschler

Hasham

Tomer

2011

Clinic Rev Allerg Immunol

Self Cite

106

View full text Add to dashboard Cite

Significant progress has been made in our understanding of the mechanisms leading to autoimmune thyroid diseases (AITD). For the first time we are beginning to unravel these mechanisms at the molecular level. AITD, including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are common autoimmune diseases affecting the thyroid. They have a complex etiology that involves genetic and environmental influences. Seven genes have been shown to contribute to the etiology of AITD. The first AITD gene discovered, HLA-DR3, is associated with both GD and HT. More recently this association was dissected at the molecular level when it was shown that substitution of the neutral amino acids Ala or Gln with arginine at position beta 74 in the HLA-DR peptide binding pocket is the specific sequence change causing AITD. Non-MHC genes that confer susceptibility to AITD can be classified into two groups: 1) immune regulatory genes (e.g. CD40, CTLA-4, PTPN22); 2) thyroid specific genes -thyroglobulin, and TSH receptor genes. These genes interact with environmental factors, such as infection, likely through epigenetic mechanisms to trigger disease. In this review we summarize the latest findings on disease susceptibility and modulation by environmental factors.

show abstract

Section: Genetics and Aitdmentioning

confidence: 99%

Cutting Edge: The Etiology of Autoimmune Thyroid Diseases

Eschler

Hasham

Tomer

2011

Clinic Rev Allerg Immunol

Self Cite

106

View full text Add to dashboard Cite

show abstract

“…In this issue of Thyroid, Huber and colleagues (27) report the contribution of CNVs in three established GD susceptibility loci, CTLA4, CD40, and PTPN22. All three genes have previously demonstrated strong association with GD and encode molecules vital in antigen presentation and control of lymphocyte activation.…”

mentioning

confidence: 99%

“…Notably, the WTCCC identified a similar phenomenon in which cell line-derived DNA displayed more variance in the raw data amplification plots (26). Based on their findings, the association analyses conducted by Huber et al (27) used DNA derived from whole blood to avoid potential inaccuracies in CNV genotyping. In the context of GD genetics, the study by Huber et al (27) represents the first attempt to specifically investigate the role of CNVs in GD and highlights some of the key challenges of CNV association analysis.…”

mentioning

confidence: 99%

Copy Number Variation in Common Disease

Brand

Gough

2011

Thyroid

View full text Add to dashboard Cite

“…[ 19 ] However, few published papers reported whether copy number variations of genes could affect the predisposition of GD. [ 4 , 5 , 20 , 21 ]…”

Section: Discussionmentioning

confidence: 99%

Copy number variations exploration of multiple genes in Graves’ disease

Song

Shao²,

Li³

et al. 2017

Medicine

View full text Add to dashboard Cite

Background:Few previous published papers reported copy number variations of genes could affect the predisposition of Graves’ disease (GD). Herein, the aim of this study was to explore the association between copy number variations (CNV) profile and GD.Methods:The preliminary copy number microarray used to screen copy number variant genes was performed in 6 GD patients. Five CNV candidate genes (CFH, CFHR1, KIAA0125, UGT2B15, and UGT2B17) were then validated in an independent set of samples (50 GD patients and 50 matched healthy ones) by the Accucopy assay method. The CNV of the other 2 genes TRY6 and CCL3L1 was investigated in 144 GD patients and 144 healthy volunteers by the definitive genotyping technique using the Taqman quantitative polymerase-chain-reaction (Taqman qPCR). TRY6 gene-associated single nucleotide polymorphism (SNP), rs13230029, was genotyped by the PCR-ligase detection reaction (LDR) in 675 GD patients and 898 healthy controls.Results:There were no correlation of the gene copy number (GCN) of CFH, CFHR1, KIAA0125, UGT2B15, and UGT2B17 with GD. In comparison with that of controls, the GCN distribution of TRY6 and CCL3L1 in GD patients did not show significantly differ (P > 0.05). Furthermore, TRY6-related polymorphism (rs13230029) showed no difference between GD patients and controls. No correlation was found between CNV or SNP genotype and clinical phenotypes. Generally, there were no link of the copy numbers of several genes, including CFH, CFHR1, KIAA0125, UGT2B15, UGT2B17, TRY6, and CCL3L1 to GD.Conclusion:Our results clearly indicated that the copy number variations of multiple genes, namely CFH, CFHR1, KIAA0125, UGT2B15, UGT2B17, TRY6, and CCL3L1, were not associated with the development of GD.

show abstract

Analysis of Immune Regulatory Genes' Copy Number Variants in Graves' Disease

Cited by 12 publications

References 27 publications

Cutting Edge: The Etiology of Autoimmune Thyroid Diseases

Cutting Edge: The Etiology of Autoimmune Thyroid Diseases

Copy Number Variation in Common Disease

Copy number variations exploration of multiple genes in Graves’ disease

Contact Info

Product

Resources

About