Endocrine Abstracts (2009) 19 P372

Confirmation of the chromosome 2q37 region as a susceptibility locus for Graves' disease

P Newby, O Pickles, J Franklyn, S Gough & M Simmonds


University of Birmingham, Birmingham, UK.


Genome wide association (GWA) studies have revolutionised the search for new susceptibility loci for complex diseases such as Graves’ disease (GD), by confirming association of known genes and identifying several novel susceptibility loci. The high density lipoprotein binding protein (HDLBP) on chromosome 2q37 is one such novel locus recently identified by the WTCCC as part of a 14 500 nonsynonymous single nucleotide polymorphisms (SNP) screen performed in 900 UK Caucasian GD patients and 1500 control subjects, with association detected with the rs7578199 SNP (P=6.9×10−4, OR=1.26). To confirm association of HDLBP with GD we genotyped rs7578199 in an extended dataset comprising a further 1404 GD and 1284 matched controls. All subjects gave informed written consent and the project was approved by the local research ethics committee. When combining the two datasets, providing 2504 GD patients and 2784 control subjects in total, association was still present between rs7578199 and GD (P=0.028, OR=1.10). To further screen this region 14 Tag SNPs were selected to capture the majority of common variation within HDLBP and screened in the extended dataset. Association was detected between the rs11680329 (P=0.015, OR=1.11) and rs6437249 (P=0.042, OR=1.10) SNPs and GD. No association was seen for any of the 12 remaining SNPs and no correlations with clinical features were detected. Although this study has confirmed that HDLBP could contribute towards GD development further screening within this region is required to localise the primary effect. Interestingly PDCD1 which we have previously shown to be weakly associated with GD is located approximately 500 kb away from HDLBP suggesting that chromosome 2q37 harbours associations with GD. This study highlights the effectiveness of GWA studies for identifying novel regions of association with disease without prior hypothesis, such as chromosome 2q37, and will be key to identifying the remainder of the genetic contribution to complex disease.

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