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
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.