Screening of SNPs at 18 positional candidate genes, located within the GD-1 locus on chromosome 14q23-q32, for susceptibility to Graves' disease: a TDT study

被引:25
作者
Chistiakov, DA [1 ]
Savost'anov, KV
Turakulov, RI
机构
[1] Katholieke Univ Leuven, Aquat Ecol Lab, Louvain, Belgium
[2] Fed Res Ctr GosNIIgenet, Dept Mol Diagnost, Moscow, Russia
[3] Endocrinol Res Ctr, Moscow, Russia
[4] Univ Queensland, Australian Genome Res Facil, Brisbane, Qld, Australia
基金
俄罗斯基础研究基金会;
关键词
GD-1; locus; Graves' disease; type II iodothyronine deiodinase; susceptibility;
D O I
10.1016/j.ymgme.2004.07.011
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Graves' disease (GD) is a complex autoimmune thyroid disorder with a strong genetic component. Genome-wide screens resolved several susceptibility loci that contribute to the development of GD. One of the susceptibility loci (GD-1 locus) was mapped on chromosome 14q31. However, a susceptibility gene located within the GD-1 locus remains undefined. Here we screen eighteen single nucleotide polymorphisms (SNPs), each is situated at a corresponding positional candidate gene, located within the GD-1 susceptibility locus on chromosome 14q23-q32, for predisposition to GD using the transmission disequilibrium test in 126 simplex Russian families affected with GD. Among SNPs tested, a significant preferential transmission of the Ala allele (41 transmissions vs. 17 nontransmissions, corrected P = 0.031) of the Thr92A1a SNP within the DIO2 gene, encoding type II iodothyronine deiodinase, from parents to affected children was found in a Russian family data set. The Thr92A1a SNP of the DIO2 gene and the D727E substitution of the thyrotropin receptor (TSHR) gene have been found to be in pair-wise linkage disequilibrium. The A92/E727 haplotype showed significant preferential transmission from parents to affected sibling (17 transmissions vs. 8 nontransmissions, P = 0.039) in simplex families. This suggests that the Thr92A1a variant of the DIO2 gene is associated or may be in linkage disequilibrium with a functional DIO2 polymorphism which involves in the development of GD in a Russian population. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:264 / 270
页数:7
相关论文
共 46 条
[1]   Association of autoimmune thyroid disease with microsatellite markers for the thyrotropin receptor gene and CTLA-4 in Japanese patients [J].
Akamizu, T ;
Sale, MM ;
Rich, SS ;
Hiratani, H ;
Noh, JY ;
Kanamoto, N ;
Saijo, M ;
Miyamoto, Y ;
Saito, Y ;
Nakao, K ;
Bowden, DW .
THYROID, 2000, 10 (10) :851-858
[2]   Lack of association between polymorphism of the thyrotropin receptor gene and Graves' disease in United Kingdom and Hong Kong Chinese patients: Case control and family-based studies [J].
Allahabadia, A ;
Heward, JM ;
Mijovic, C ;
Carr-Smith, J ;
Daykin, J ;
Cockram, C ;
Barnett, AH ;
Sheppard, MC ;
Franklyn, JA ;
Gough, SCL .
THYROID, 1998, 8 (09) :777-780
[3]  
Ban Y, 2001, BMC Med Genet, V2, P1, DOI 10.1186/1471-2350-2-1
[4]   A germline single nucleotide polymorphism at the intracellular domain of the human thyrotropin receptor does not have a major effect on the development of Graves' disease [J].
Ban, Y ;
Greenberg, DA ;
Concepcion, ES ;
Tomer, Y .
THYROID, 2002, 12 (12) :1079-1083
[5]   SEL1L microsatellite polymorphism in Japanese patients with autoimmune thyroid diseases [J].
Ban, Y ;
Taniyama, M ;
Tozaki, T ;
Yanagawa, T ;
Tomita, M ;
Ban, Y .
THYROID, 2001, 11 (04) :335-338
[6]   Linkage analysis of candidate genes in autoimmune thyroid disease: 1. Selected immunoregulatory genes [J].
Barbesino, G ;
Tomer, Y ;
Concepcion, E ;
Davies, TF ;
Greenberg, DA .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (05) :1580-1584
[7]   Characterization of the 5′-flanking and 5′-untranslated regions of the cyclic adenosine 3′,5′-monophosphate-responsive human type 2 iodothyronine deiodinase gene [J].
Bartha, T ;
Kim, SW ;
Salvatore, D ;
Gereben, B ;
Tu, HM ;
Harney, JW ;
Rudas, P ;
Larsen, PR .
ENDOCRINOLOGY, 2000, 141 (01) :229-237
[8]   TYPE-I IODOTHYRONINE DEIODINASE IS A SELENOCYSTEINE-CONTAINING ENZYME [J].
BERRY, MJ ;
BANU, L ;
LARSEN, PR .
NATURE, 1991, 349 (6308) :438-440
[9]   Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases [J].
Bianco, AC ;
Salvatore, D ;
Gereben, B ;
Berry, MJ ;
Larsen, PR .
ENDOCRINE REVIEWS, 2002, 23 (01) :38-89
[10]   The role of selenocysteine 133 in catalysis by the human type 2 iodothyronine deiodinase [J].
Buettner, C ;
Harney, JW ;
Larsen, PR .
ENDOCRINOLOGY, 2000, 141 (12) :4606-4612