Multiple SNPs in intron 41 of thyroglobulin gene are associated with autoimmune thyroid disease in the Japanese population.
BACKGROUND
The etiology of the autoimmune thyroid diseases (AITDs), Graves' disease (GD) and Hashimoto's thyroiditis (HT), is largely unknown. However, genetic susceptibility is believed to play a major role. Two whole genome scans from Japan and from the US identified a locus on chromosome 8q24 that showed evidence for linkage with AITD and HT. Recent studies have demonstrated an association between thyroglobulin (Tg) polymorphisms and AITD in Caucasians, suggesting that Tg is a susceptibility gene on 8q24.


OBJECTIVE
The objective of the study was to refine Tg association with AITD, by analyzing a panel of 25 SNPs across an extended 260 kb region of the Tg.


METHODS
We studied 458 Japanese AITD patients (287 GD and 171 HT patients) and 221 matched Japanese control subjects in association studies. Case-control association studies were performed using 25 Tg single nucleotide polymorphisms (SNPs) chosen from a database of the Single Nucleotide Polymorphism Database (dbSNP). Haplotype analysis was undertaken using the computer program SNPAlyze version 7.0.


CONCLUSIONS
In total, 5 SNPs revealed association with GD (P<0.05), with the strongest SNP associations at rs2256366 (P = 0.002) and rs2687836 (P = 0.0077), both located in intron 41 of the Tg gene. Because of the strong LD between these two strongest associated variants, we performed the haplotype analysis, and identified a major protective haplotype for GD (P = 0.001). These results suggested that the Tg gene is involved in susceptibility for GD and AITD in the Japanese.
Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan. yshyban@yahoo.co.jp
Yoshiyuki
Y
Ban
Teruaki
T
Tozaki
Matsuo
M
Taniyama
Luce
L
Skrabanek
Yasuko
Y
Nakano
Yoshio
Y
Ban
Tsutomu
T
Hirano
D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics*; D006239:Haplotypes; D050031:Hashimoto Disease / Q000235:genetics*; D006801:Humans; D007438:Introns; D007564:Japan; D020641:Polymorphism, Single Nucleotide; D013954:Thyroglobulin / Q000235:genetics*
D013954:Thyroglobulin