Functional SNPs in the SCGB3A2 promoter are associated with susceptibility to Graves' disease

Song, Huai-Dong; Liang, Jun; Shi, Jingyi; Zhao, Shuang‐Xia; Li, Zhi; Zhao, Jiajun; Peng, Yongde; Gao, Guan-Qi; Tao, Jiong; Pan, Chun-Ming; Shao, Li; Cheng, Feng; Wang, Yi; Yuan, Guoyue; Xu, Chao; Han, Bing; Huang, Wei; Chu, Xun; Chen, Yi; Yan, Sheng; Li, Rong-Ying; Su, Qing; Gao, Ling; Wang, Jia; Li, Jin; Chen, Ming-Dao; Chen, Sai‐Juan; Chen, Zhu; Chen, Jialun

doi:10.1093/hmg/ddn442

Cited by 45 publications

(54 citation statements)

References 38 publications

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“…In this study, we confirmed a role of the SCGB3A2 −112G>A polymorphism as a marker for GD susceptibility on chromosome 5q31-q33 that was previously shown by Song et al (2009) andSimmonds et al (2010). An association between the allele A and GD (OR=1.33, P=2.9×10 −5 ) observed in a Russian population was stronger than the size of effect of the carriage of this allele on susceptibility to GD in UK Caucasians (OR=1.18, P=0.007) (Simmonds et al 2010).…”

Section: Discussionsupporting

confidence: 88%

“…Association between marker rs31480 of IL-3 and GD was not confirmed in a recent well-powered study of British Caucasians (Simmonds et al 2010). However, Simmonds et al (2010) replicated findings of Song et al (2009), who showed an association between GD and marker rs1368408 located in the promoter of the secretoglobin 3A2 (SCGB3A2) gene, in three independent Chinese population datasets. The human SCGB3A2 gene is assigned to chromosome 5q31-32 (Niimi et al 2001).…”

Section: Introductionsupporting

confidence: 68%

“…The human SCGB3A2 gene is assigned to chromosome 5q31-32 (Niimi et al 2001). Therefore, the data presented by Song et al (2009) andSimmonds et al (2010) suggest for a likely role of SCGB3A2 as a susceptibility gene for GD on chromosome 5q31-33.…”

Section: Introductionmentioning

confidence: 96%

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The −112G > A polymorphism of the secretoglobin 3A2 (SCGB3A2) gene encoding uteroglobin-related protein 1 (UGRP1) increases risk for the development of Graves’ disease in subsets of patients with elevated levels of immunoglobulin E

et al. 2010

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The human secretoglobin 3A2 (SCGB3A2) gene encoding secretory uteroglobin-related protein 1 (UGRP1) resides on the chromosome region 5q31-33 that harbors a susceptibility locus to several autoimmune and inflammatory diseases, including asthma and Graves' disease (GD). Recently, association between the marker rs1368408 (-112G >A), located in the promoter region of the SCGB3A2 gene, and susceptibility to GD was found in Chinese and UK Caucasians. The study aim was to evaluate whether this polymorphism confers GD susceptibility in a large population cohort comprising 1,474 Russian GD patients and 1,619 controls. The marker rs1368408 was studied using a TaqMan allele discrimination assay. Serum levels of UGRP1 and immunoglobulin E (IgE) were assessed using enzyme-linked immunosorbent assay (ELISA) analyses. Association between the allele A of SCGB3A2 and a higher risk of GD (odds ratio [OR] = 1.33, P = 2.9 × 10(-5)) was shown. Both affected and non-affected carriers of the higher risk genotype A/A had significantly decreased levels of serum UGRP1 compared to the subjects homozygous for G/G (93 ± 37 pg/ml vs. 132 ± 45 pg/ml, P = 0.0011 for GD patients; 77 ± 28 pg/ml vs. 119 ± 33 pg/ml, P = 0.0019 for controls). Serum IgE levels were significantly higher in non-affected subjects homozygous for A/A compared to control individuals homozygous for G/G (153 ± 46 IU/ml vs. 122 ± 40 IU/ml, P = 0.0095). Our data suggest that the carriage of the SCGB3A2 -112A/A variant increases the risk for GD in subsets of patients with elevated levels of IgE, a hallmark of allergic asthma. Therefore, the SCGB3A2 -112G >A polymorphism may be considered as a likely marker linking susceptibility to allergy/asthma and GD on chromosome 5q31-33.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionsupporting

confidence: 68%

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The −112G > A polymorphism of the secretoglobin 3A2 (SCGB3A2) gene encoding uteroglobin-related protein 1 (UGRP1) increases risk for the development of Graves’ disease in subsets of patients with elevated levels of immunoglobulin E

et al. 2010

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“…Similarly, UGRP1 has been suggested to exhibit anti-inflammatory functions. It has been shown that UGRP1 is associated with an increased risk for Graves’ disease (17,18). However, there have been confounding results with regard to the correlation between UGRP1 gene polymorphisms and asthma risk (5,7,9,19).…”

Section: Discussionmentioning

confidence: 99%

Association between the -112G/A polymorphism of uteroglobulin-related protein 1 gene and asthma risk: A meta-analysis

Xie

Shen

et al. 2014

Experimental and Therapeutic Medicine

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The aim of this study was to investigate the correlation between the -112G/A polymorphism of the uteroglobulin-related protein 1 (UGRP1) gene and asthma risk using meta-analysis. PubMed, BIOSIS Previews and EBSCOhost were searched, and data were extracted independently by two reviewers. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the associations. Statistical analysis was performed using Review Manager 5.2 and STATA 11.0 software. Six studies, involving 816 cases and 1,165 controls, were included in the analysis. The meta-analysis showed a significant correlation between the UGRP1-112G/A polymorphism and asthma for AA versus GG (P=0.01) and AA versus GA/GG (P=0.02). Furthermore, stratification by ethnicity revealed a significant correlation between the -112G/A polymorphism and asthma for A versus G (P=0.02), AA versus GG (P=0.01) and AA versus GA/GG (P=0.03) in Asians, but not in Caucasians. When stratified by atopy, a significant correlation was observed for A versus G (P=0.02) and AA/GA versus GG (P=0.04) in the mixed group. No correlation was observed for age stratification. Results of the current meta-analysis indicate that the -112G/A polymorphism of the UGRP1 gene is likely to contribute to asthma risk, particularly in the Asian population.

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“…Increasing attention has previously been paid to the CT60 SNP of CTLA4 in patients with GD (26)(27)(28). However, the correlation between CT60 A/G and the development of GD varied among patients from different geographic populations (29). Thus, there are limited reports regarding an association between the CT60 SNP and GD in the Han population of Southern China.…”

Section: Introductionmentioning

confidence: 99%

Association of the CTLA4 gene CT60/rs3087243 single-nucleotide polymorphisms with Graves' disease

Fang

Zhang

et al. 2015

Biomedical Reports

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Abstract. It has been widely reported that the CT60 single-nucleotide polymorphism (SNP), which is in the 3'-untranslated region of the cytotoxic T lymphocyte associated 4 (CTLA4) gene, is strongly correlated with certain immune-mediated diseases. The present case-control study aimed to investigate the genetic association between the CT60 SNP within the CTLA4 gene and Graves' disease (GD). A total of 288 patients with GD and 290 control subjects were recruited for the study. The CT60 SNP of the CTLA4 gene was detected by direct DNA sequencing. The results indicated that the frequencies of the GG genotype and G allele in the case group were evidently higher than that in the control group (P=4x10 , respectively). Furthermore, the G/G genotype of the CT60 SNP was associated with an increased risk for GD (odds ratio=2.223). In conclusion, these results suggested that the CT60 SNP is associated with susceptibility to GD. The frequency of the disease-susceptible G allele of CT60 was significantly associated with an increased risk of GD development. IntroductionGraves' Disease (GD), also known as toxic diffuse goiter, can increase the level of thyroid hormone, is one of the organ-specific autoimmune diseases and it accounts for 85% of all clinical hyperthyroidism (1,2). The disease often presents in patients aged from 20-40 years old, with a male to female ratio of ~1:8 and a significant familial tendency (3). The clinical performance of GD is not limited to the thyroid, but is a multi-system syndrome, including the high metabolic syndrome group, diffuse goiter, eye symptoms, lesions and thyroid extremity diseases (4-6). Immunologically, GD is characterized by increased circulating antibodies against thyroid-stimulating hormone receptor (TSHR), thyroglobulin (TG) and thyroid peroxidase (TPO). Although the precise pathogenesis involved in the process of GD is not completely understood, certain findings indicate that complex interactions between environmental, genetic, endogenous and local factors are involved in its pathogenesis (7-9). A study on the genetic susceptibility genes of GD has become of interest (10-13).Previous studies have demonstrated that a number of susceptibility genes are associated with the autoimmune thyroid diseases, including interleukin-21, TSHR, human leukocyte antigen class I and II, cluster of differentiation 40 (CD40) and cytotoxic T lymphocyte associated 4 (CTLA4) (10-15). Among them, CTLA4 as a key negative regulator of the T lymphocyte immune response has attracted an increasing focus on the susceptibility to autoimmune disease. CTLA4, which is expressed by activate T cells, is a type of transmembrane protein. The CTLA4 gene is located on human chromosome 2q33 (16). The most significant function of the CTLA4 gene is negative regulation of the human immune response. Several polymorphic sites in the CTLA4 gene are associated with thyroid diseases, such as -318C/T promoter and 49A/G exon 1, -224(AT)n dinucleotide repeat sequence single-nucleotide polymorphism (SNP), -1722C/T, -1661A/G, CT60 (...

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Functional SNPs in the SCGB3A2 promoter are associated with susceptibility to Graves' disease

Cited by 45 publications

References 38 publications

The −112G > A polymorphism of the secretoglobin 3A2 (SCGB3A2) gene encoding uteroglobin-related protein 1 (UGRP1) increases risk for the development of Graves’ disease in subsets of patients with elevated levels of immunoglobulin E

The −112G > A polymorphism of the secretoglobin 3A2 (SCGB3A2) gene encoding uteroglobin-related protein 1 (UGRP1) increases risk for the development of Graves’ disease in subsets of patients with elevated levels of immunoglobulin E

Association between the -112G/A polymorphism of uteroglobulin-related protein 1 gene and asthma risk: A meta-analysis

Association of the CTLA4 gene CT60/rs3087243 single-nucleotide polymorphisms with Graves' disease

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