Skip Navigation



Human Molecular Genetics Advance Access published online on January 6, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddn442
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
18/6/1156    most recent
ddn442v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Song, H.-D.
Right arrow Articles by Chen, J.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Song, H.-D.
Right arrow Articles by Chen, J.-L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Huai-Dong Song1,2,§,*, Jun Liang3,§,+, Jing-Yi Shi1,§, Shuang-Xia Zhao1,§, Zhi Liu1,§, Jia-Jun Zhao3,§, Yong-De Peng4, Guan-Qi Gao5, Jiong Tao1, Chun-Ming Pan1, Li Shao1, Feng Cheng1, Yi Wang6, Guo-Yue Yuan7, Chao Xu1, Bing Han1, Wei Huang8, Xun Chu8, Yi Chen1, Yan Sheng1, Rong-Ying Li1, Qing Su9, Ling Gao3, Wei-Ping Jia10, Li Jin6, Ming-Dao Chen1, Sai-Juan Chen1,2, Zhu Chen1,2 and Jia-Lun Chen1

1 Ruijin Hospital, State Key Laboratory of Medical Genomics, Molecular Medicine Center Shanghai Institute of Endocrinology, Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai 20025, China 2 Shanghai Center for Systems Biomedicine, SJTU, 800 Dong Chuan Road, Shanghai, 200240, China 3 Department of Endocrinology, Shandong Province Hospital, Shandong University, 324 Jing 5 Road, Jinan 250021, China 4 Department of Endocrinology, The First People's Hospital Affiliated to the Shanghai Jiaotong University, Shanghai 200080, China 5 Department of Endocrinology, The People's Hospital of Lingyi, Shandong Province, 27 Liberation Road, Lingyi 276003, China 6 Centre of anthropology, Fudan University, 220 Handan Road, Shanghai 200433, China 7 Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China 8 Chinese National Human Genome Center at Shanghai, 250 Bi Bo Road, Zhang Jiang High Tech Park, Shanghai 201203, China 9 Department of Endocrinology, Xin Hua Hospital, Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai 20092, China 10 Shanghai Diabetes Institute, No. 6 Hospital Affiliated to the Shanghai Jiaotong University, Shanghai 200233, China

* To whom correspondence should be addressed at State Key Laboratory of Medical Genomics, Molecular Medicine Center Shanghai Institute of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai 20025, China. Tel: 8621-64370045-610808; Fax: 8621-64743206; E-mail huaidong_s1966{at}163.com

Received November 14, 2008; Revised December 22, 2008; Accepted December 30, 2008

Graves’ disease (GD) is one of the most common human autoimmune diseases, and recent data estimated a prevalence of clinical hyperthyroidism of 0.25 to 1.09% in the population. Several reports have linked GD to the region 5q12-q33; and a locus between markers D5s436 and D5s434 was specifically linked to GD susceptibility in the Chinese population. In the present study, association analysis was performed using a large number of single nucleotide polymorphisms (SNPs) at this locus in 2811 patients with GD recruited from different geographic regions of China. The strongest associations with GD in the combined Chinese Han cohorts were mapped to two SNPs in the promoter (pSNP) of SCGB3A2 (SNP76, rs1368408, p=1.43x10–6, odds ratio=1.28 and SNP75, -623~-622, p=7.62x10–5, odds ratio=1.32, respectively), a gene implicated in immune regulation. On the other hand, pSNP haplotypes composed of the SNP76 (rs1368408)+SNP74 (rs6882292) or SNP76+SNP75 (-623~-622, AG/T) variants are correlated with high disease susceptibility (p=0.0007, and p=0.0192, respectively) in this combined Chinese Han cohort. Furthermore, these haplotypes were associated with reduced SCGB3A2 gene expression levels in human thyroid tissue, while functional analysis revealed a relatively low efficiency of SCGB3A2 promoters of the SNP76+SNP75 and SNP76+SNP74 haplotypes in driving gene expression. These results suggest that the SCGB3A2 gene may contribute to GD susceptibility.

§ These authors contributed equally to this work.

+ The present address: Department of Endocrinology, the Fourth Hospital of Xuzhou, Jiangsu Province.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.