Genome-Wide Scan of Graves’ Disease: Evidence for Linkage on Chromosome 5q31 in Chinese Han Pedigrees

Jin, Ying; Wang, Teng; Ben, Songtao; Xiong, Xiaoyan; Zhang, Jing; Xu, Shijie; Shugart, Yin Yao; Jin, Li; Chen, Jialun; Huang, Wei

doi:10.1210/jc.2001-011980

Cited by 51 publications

(51 citation statements)

References 48 publications

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“…Therefore, IL-12 may play a role in the pathogenesis of GD and GO. Recent genome-wide researches have provided evidence for the linkage of GD to loci on chromosome 5 in regions 5q31-q33 in Japanese [15] and Chinese [16] populations. This region encodes a cluster of cytokine genes, including IL-3, IL-4, IL-5, IL-9, IL-12B and IL-13, which are involved in inflammation and IgE synthesis [19].…”

Section: Discussionmentioning

confidence: 99%

“…Recent genome-wide researches have provided evidence for the linkage of GD to loci on multiple chromosomes, including loci on chromosome 5 in regions 5q31-q33 [15,16], which have been linked to autoimmune thyroid disorders including GD in Japanese and Chinese populations, but not in Caucasian popu-lations. This might suggest that these loci are specific to East Asian populations.…”

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confidence: 99%

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Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

et al. 2006

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Abstract. Graves' disease (GD) is an autoimmune disorder with genetic predisposition and frequently associated with Graves' ophthalmopathy (GO). Interleukin 12 (IL-12) is an important mediator of inflammatory immune responses and is expressed in the thyroid and orbit. IL-12B gene, which encodes the p40 subunit of IL-12, is located at chromosome 5q31-33. The aim of the present study was to investigate whether IL-12B gene polymorphism is associated with the development of GD or GO. IL-12B gene polymorphism was studied in Japanese GD patients (n = 329) and healthy control subjects without anti-thyroid autoantibodies or a family history of autoimmune disorders (n = 226). The A/C polymorphism at position 1188 of the 3' untranslated region (3'UTR) of the IL-12B gene was analyzed using the polymerase chain reaction -restriction fragment length polymorphism method. There was no difference in allele or genotype frequency of the IL-12B gene polymorphism (1188A/C) between GD patients and control subjects. There was no association of the IL-12B gene polymorphism with ophthalmopathy, severity of hyperthyroidism or serum IgE levels. There was no association of the IL-12B gene polymorphism with serum IL-12 levels, which were significantly elevated in hyperthyroid phase of GD. In conclusion, IL-12B gene 1188A/C polymorphism is not associated with GD or GO susceptibility in Japanese.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

et al. 2006

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“…Our previous study mapped the susceptible gene of GD in chromosomal 5q31 regions using 54 Chinese Han multiple pedigrees (Jin et al 2003). Meanwhile, Sakai and co-workers mapped susceptibility loci for Hashimoto thyroiditis (HT), another autoimmune thyroid disease, to 8q23-q24, and for AITD (autoimmune thyroid disease, i.e., GD and HT) to 5q31-q33 by multipoint linkage analysis in a collection of Japanese AITD affected sib-pairs (Sakai et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Association study between the IL4, IL13, IRF1 and UGRP1 genes in chromosomal 5q31 region and Chinese Graves’ disease

Sun

Jin

et al. 2005

J Hum Genet

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Graves' disease (GD) was believed to be a polygenic disease. Several chromosomal regions were linked to GD, and the 5q31 chromosome regions containing several interleukin genes cluster were worth observing. In this study, IL4, IL13, IRF1 and UGRP1 genes were sequenced, and 5, 3, 7 and 7 polymorphisms respectively were discovered. Then an extended association study for the attracting polymorphisms was performed with 146 sporadic Graves' patients, 142 unrelated controls and the 54 multiplex Graves' families. However, the genotype and allele frequency distribution of these polymorphisms had similar distribution between the Graves' patients and unrelated controls, and transmission disequilibrium tests indicated that none of them showed dominant transmission from heterozygous parents to the affected offsprings. Comparison of the clinical variables of the Graves' patients indicated that the onset ages of the patients carrying TT at IRF1 6477 T/G locus were younger than those having variant allele (TG, GG); the difference was of statistical significance (P=0.005, Pc=0.020). Our association study revealed that, IL4, IL13, IRF1 and UGRP1 genes in chromosomal 5q31 regions might not confer susceptibility to Chinese GD. But those individuals who were TT homozygous at IRF1 6477 T/G locus seemed to be attacked by GD much earlier than others.

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“…We and others have earlier implicated chromosomal region 5q31-33 for contributing to the genetic susceptibility to GD in East-Asian populations. [3][4][5] The linkage peak in our earlier linkage analysis was within an approximate 2 cM interval between markers D5S436 and D5S4343. The multipoint LOD scores throughout this interval were more than 3.0, with a maximum multipoint LOD score of 4.12.…”

Section: Introductionmentioning

confidence: 80%

“…Linkage to chromosome 5q31-33 has only been detected in two Asian GD genome screens 3,4 and has failed to be detected in two Caucasian genome screens. 21,22 In addition, association analysis using microsatellite markers confirmed evidence for the presence of susceptibility genes in or near 5q23-q33 in a Japanese cohort.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2009

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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 0 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 (OR common ) ¼ 1.63, combined P (P comb ) ¼ 4 Â 10 À6 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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Genome-Wide Scan of Graves’ Disease: Evidence for Linkage on Chromosome 5q31 in Chinese Han Pedigrees

Cited by 51 publications

References 48 publications

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

Association study between the IL4, IL13, IRF1 and UGRP1 genes in chromosomal 5q31 region and Chinese Graves’ disease

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

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