title: 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.
abstract: 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 Thr92Ala SNP within the DIO2 gene, encoding type II iodothyronine deiodinase, from parents to affected children was found in a Russian family data set. The Thr92Ala 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 Thr92Ala 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.
authors.affiliation: Laboratory of Aquatic Ecology, Katholieke Universiteit Leuven, Leuven, Belgium. dimitry.chistiakov@bio.kuleuven.ac.be
authors.forename: D A
authors.initials: DA
authors.lastname: Chistiakov
authors.forename: K V
authors.initials: KV
authors.lastname: Savost'anov
authors.forename: R I
authors.initials: RI
authors.lastname: Turakulov
mesh_terms: D000293:Adolescent; D000328:Adult; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006111:Graves Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011989:Receptors, Thyrotropin / Q000235:genetics; D012426:Russia; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D017931:DNA Primers; D007453:Iodide Peroxidase; D011989:Receptors, Thyrotropin; D000097564:Iodothyronine Deiodinase Type II