Two major genes, linked to HLA and Gm, control susceptibility to Graves' disease

Uno, Hisamitsu; Sasazuki, Takehiko; Tamai, Hiroshi; Matsumoto, Hideo

doi:10.1038/292768a0

Cited by 170 publications

(71 citation statements)

References 12 publications

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“…In addition to a strong contribution to susceptibility by theHLA locus (Uno et al 1981;Dong et al 1992;Wan et al 1995), GD and HT have been reported to be associated and/or linked to the CTLA4 locus (Yanagawa et al 1995;Donner et al 1997;Kotsa et al 1997;Heward et al 1999;Vaidya et al 1999a, b). However, the causal polymorphism(s) at this locus remained to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Association of the T-cell regulatory gene CTLA4 with Graves’ disease and autoimmune thyroid disease in the Japanese

et al. 2004

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Autoimmune thyroid disease (AITD) is caused by an immune response to self-thyroid antigen. The cytotoxic T-lymphocyte antigen-4 (CTLA4) gene, encoding a negative regulator of the T-lymphocyte immune response, had been reported to be associated and/ or linked to AITD. Recently, AITD susceptibility in the Caucasians was mapped to the 6.1-kb 3¢UTR of the CTLA4 gene, in which the three single-nucleotide polymorphisms (SNPs) CT60, JO31, and JO30 were strongly associated with AITD. In order to determine the association of the CTLA4 gene with AITD in the Japanese, case-control association analysis for the four SNPs of the CTLA4 gene using 380 AITD patients and 266 healthy controls was done. Among the SNPs examined, the SNP JO31 was most significantly associated with AITD in the Japanese, whereas the association of the JO30 with AITD was not observed. The frequency of the disease-susceptible G allele of the JO31 of the Japanese control was higher than that of the Caucasians (67.1% vs 50.2%); however, the G allele of the JO31 was associated with Graves' disease (GD) (67.1% vs 76.3%, P=0.0013) and AITD in the Japanese (67.1% vs 74.2%, P=0.0055). Furthermore, the G allele of the JO31 was associated with the increased risk for GD [P=0.0051, odds ratio (OR)=1.7] and AITD (P=0.016, OR=1.5) in a dominant model. These results suggested that the CTLA4 gene is involved in the susceptibility for GD and AITD in the Japanese.

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Section: Introductionmentioning

confidence: 99%

Association of the T-cell regulatory gene CTLA4 with Graves’ disease and autoimmune thyroid disease in the Japanese

et al. 2004

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“…Graves disease has been suggested as a candidate for the two-locus mode of inheritance (Uno et aL, 1981). In Table 5, segregation distribution were shown for eight nuclear families whose both parents were healthy and for seven families whose one of parents was affected.…”

Section: Numerical Example and Discussionmentioning

confidence: 99%

“…In the following illustration, the values of nsr were taken from Table 5 (data), P(r) and u-scores were from Table A3. For example, the total scores for U and K under the null hypothesis of single recessives that H0: p=1/4, k=0, ~r=0, were calculated as follows: (Uno et al, 1981 ;Sasazuki et al, 1982). Two genetic models have been proposed in Graves disease by the affected sibpair method : (i) an HLA-linked recessive gene with frequency 0.30 and a Gm-linked recessive gene with frequency 0.10; and (ii) an HLA-linked dominant gene with frequency 0.08 and a Gm-linked recessive gene with frequency 0.10.…”

Section: Numerical Example and Discussionmentioning

confidence: 99%

“…There is evidence that coeliac disease is the result of two recessive loci (Greenberg and Lange, 1982;Kagnoff, 1982). Hyperlipoproteinemia is the result of two loci (Utermann et al, 1980), Graves disease (Uno et al, 1981) and insulin-dependent diabetes meUitus (Thomson, 1980;Nakao et al, 1981) have both suggested as candidates for a two-locus mode of inheritance. It has also been suggested that other HLA-related diseases, especially autoimmune diseases, may be the result of a locus within the HLA system and a second, non-HLA linked locus (Greenberg and Anderson, 1983).…”

Section: Introductionmentioning

confidence: 99%

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Complex segregation analysis for two-locus model: Autosomal double recessive

Yasuda¹,

Sasazuki

1984

Jap J Human Genet

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“…Several genetic factors associated with AITD have been tentatively identified by candidate-gene and genome-scanning approaches. They include HLA, cytotoxic T-lymphocyteassociated-4 (CTLA-4), and TSHR gene, and other chromosomal regions, such as 14q31 (GD-1), 20q11.2 (GD-2), Xq21.33-22 (GD-3), 13q32 (HT-1), 12q22, 18q21 (IDDM 6), and Xp11 (Farid et al 1979;Uno et al 1981;Yanagawa et al 1995;Donner et al 1997;Vaidya et al 1999;Barbesino et al 1998;Tomer et al 1999;Vaidya et al 2000;Sale et al 1997;Akamizu et al 2000). Evidence for AITD genes, however, varies among researchers or populations, and no consensus has been obtained.…”

Section: Introductionmentioning

confidence: 99%

Association study of autoimmune thyroid disease at 5q23-q33 in Japanese patients

et al. 2003

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As part of a genome scan to locate familial Graves' disease (GD) and Hashimoto's thyroiditis (HT) genes, an autoimmune thyroid disease (AITD) susceptibility locus has recently been identified at 5q31-q33 in a Japanese population. We performed an association study using six microsatellite markers located at this locus in a set of 440 unrelated Japanese AITD patients and 218 Japanese controls. We found significant allelic association between AITD and three markers located in 5q23-q33. GD demonstrated significant associations with two of these markers, while HT did not show significant associations with any markers. Further, when patients with GD were stratified according to clinical manifestations, the association was significantly different from the other subgroup of each category. These findings suggest the presence of susceptible genes of AITD, especially distinct subgroups of GD, in or near 5q23-q33.

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Two major genes, linked to HLA and Gm, control susceptibility to Graves' disease

Cited by 170 publications

References 12 publications

Association of the T-cell regulatory gene CTLA4 with Graves’ disease and autoimmune thyroid disease in the Japanese

Association of the T-cell regulatory gene CTLA4 with Graves’ disease and autoimmune thyroid disease in the Japanese

Complex segregation analysis for two-locus model: Autosomal double recessive

Association study of autoimmune thyroid disease at 5q23-q33 in Japanese patients

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