The association of thyroid peroxidase antibody risk loci with susceptibility to and phenotype of Graves' disease. (22nd December 2014)

• Record Type: Journal Article
• Authors: Kuś, Aleksander; Szymański, Konrad; Peeters, Robin P.; Miśkiewicz, Piotr; Porcu, Eleonora; Pistis, Giorgio; Sanna, Serena; Naitza, Silvia; Płoski, Rafał; Medici, Marco; Bednarczuk, Tomasz
• Is Part Of: Clinical endocrinology. Volume 83:Number 4(2015:Oct.)
• Page Start: 556
• Page End: 562
• Publication Date: 2014-12-22
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12640
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12640-abs-0001"> <title>Summary</title> <sec id="cen12640-sec-0001" sec-type="section"> <title>Background</title> <p>Despite great progress, the genetic basis of Graves' disease (GD) remains poorly understood. Recently, a population‐based genomewide association study (GWAS) identified five novel loci (<italic>ATXN2/SH2B3, MAGI3, BACH2, TPO</italic> and <italic>KALRN</italic>) as significantly associated with the presence of thyroid peroxidase autoantibodies (TPOAbs), whereas several other loci showed suggestive association.</p> </sec> <sec id="cen12640-sec-0002" sec-type="section"> <title>Methods</title> <p>In this study, we investigated 16 single nucleotide polymorphisms (SNPs) associated with TPOAbs for the association with susceptibility to and phenotype of GD in a cohort of 647 patients with GD and 769 controls from a Polish Caucasian population.</p> </sec> <sec id="cen12640-sec-0003" sec-type="section"> <title>Results</title> <p>SNPs within/near <italic>HCP5</italic> (rs3094228, <italic>P </italic>=<italic> </italic>1·6 × 10<sup>−12</sup>, OR = 1·88), <italic>MAGI3</italic> (rs1230666, <italic>P = </italic>1·9 × 10<sup>−5</sup>, OR = 1·51) and <italic>ATXN2/SH2B3</italic> (rs653178, <italic>P = </italic>0·0015, OR = 1·28) loci were significantly associated with susceptibility to GD. Allele frequencies differed significantly in subgroups of patients with GD stratified by age of GD onset for <italic>HCP5</italic> (<italic>P = </italic>0·0014, OR = 1·50) and showed a suggestive difference for <italic>MAGI3</italic> (<italic>P = </italic>0·0035, OR = 1·50) SNPs. Although rs11675434 located near <italic>TPO</italic> showed no association with GD susceptibility, it was significantly associated with the presence of clinically evident Graves' ophthalmopathy (GO, <italic> P = </italic>5·2 × 10<sup>−5</sup>, OR = 1·64), and this effect was independent from smoking status, age of GD onset and gender.</p> </sec> <sec id="cen12640-sec-0004" sec-type="section"> <title>Conclusions</title> <p>This is the first study showing an association of the <italic>ATXN2/SH2B3</italic> locus with susceptibility to GD. Furthermore, we observed a novel significant association within the <italic>HLA</italic> region at a SNP located near <italic>HCP5</italic> and confirmed the association of the <italic>MAGI3</italic> locus with GD susceptibility. <italic>HCP5</italic> and <italic>MAGI3</italic> SNPs were further correlated with age of GD onset. Finally, we identified <italic>TPO</italic> as a new susceptibility locus for GO.</p> </sec> </abstract>