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Polymorphisms in the interleukin 3 gene show strong association with susceptibility to Graves’ disease in Chinese population

Genes & Immunity volume 10, pages 260–266 (2009)Cite this article

Abstract

Graves’ disease (GD) is a common organ-specific autoimmune disorder, which is multifactorial and develops in genetically susceptible individuals. We had earlier mapped a susceptibility locus for GD to chromosome 5q31–33 in a linkage study. Here we used tag single-nucleotide polymorphisms (SNPs) to search for genetic variants associated with GD, and examined 19 functional candidate genes in this chromosomal region. We identified 192 polymorphisms by re-sequencing the candidate genes, and selected 51 tagSNPs to genotype in a case–control collection of 1118 south Han Chinese subjects (428 cases and 690 controls). Initial analysis suggested that a non-synonymous SNP rs40401 (P27S) of interleukin 3 (IL3) was associated with GD, and further fine-mapping showed that rs40401, or its perfect proxy SNP rs31480 in the 5′ flanking region of IL3, fully accounted for the association signal at this locus. We replicated significant association of rs40401 with GD in an independent sample collection of 839 north Han Chinese subjects. A combined analysis revealed strong validation of this association (odds ratio (ORcommon)=1.63, combined P (Pcomb)=4 × 10−6 in the Recessive disease model). This study provides convincing evidence that the IL3 gene is a susceptibility locus for GD in the Chinese population.

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Acknowledgements

We gratefully acknowledge Prof Zhu Chen for insightful instruction. This work was supported by the grants from Chinese High-Tech Program (2006AA020706, 2006AA02A406), National Key Project for Basic Research (2004CB518605), Chinese National Natural Science Fund for Distinguished Young Scholars (30625019), Shanghai Science and Technology Committee (06XD14015) and Chinese National Natural Science Fund (30771029).

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Author notes

  1. X Chu, C Dong and R Lei: These are the co-first authors.

  2. Dr W Huang, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197, Rui Jin II Road, Shanghai 200025, China

  3. Dr W Huang, Chinese National Human Genome Center, 250, Bi Bo Road, Shanghai 201203, China. E-mail: huangwei@chgc.sh.cn

Authors and Affiliations

  1. Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

    X Chu, R Lei, H Song & W Huang

  2. Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai, China

    X Chu, C Dong, L Sun, Z Wang, M Shen, Y Wang, B Wang, K Zhang, L Yang, Y Li, W Yuan, Y Wang, L Jin & W Huang

  3. Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

    Y Dong

  4. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China

    L Jin

  5. Human Genetics Center, University of Texas-Houston Health Science Centre, Houston, TX, USA

    M Xiong

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Correspondence to W Huang.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Chu, X., Dong, C., Lei, R. et al. Polymorphisms in the interleukin 3 gene show strong association with susceptibility to Graves’ disease in Chinese population. Genes Immun 10, 260–266 (2009). https://doi.org/10.1038/gene.2009.3

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