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- Title
SRGAP1 is a candidate gene for papillary thyroid carcinoma susceptibility.
- Authors
He, Huiling; Bronisz, Agnieszka; Liyanarachchi, Sandya; Nagy, Rebecca; Li, Wei; Huang, Yungui; Akagi, Keiko; Saji, Motoyasu; Kula, Dorota; Wojcicka, Anna; Sebastian, Nikhil; Wen, Bernard; Puch, Zbigniew; Kalemba, Michal; Stachlewska, Elzbieta; Czetwertynska, Malgorzata; Dlugosinska, Joanna; Dymecka, Kinga; Ploski, Rafal; Krawczyk, Marek
- Abstract
<bold>Background: </bold>Papillary thyroid carcinoma (PTC) shows high heritability, yet efforts to find predisposing genes have been largely negative.<bold>Objectives: </bold>The objective of this study was to identify susceptibility genes for PTC.<bold>Methods: </bold>A genome-wide linkage analysis was performed in 38 families. Targeted association study and screening were performed in 2 large cohorts of PTC patients and controls. Candidate DNA variants were tested in functional studies.<bold>Results: </bold>Linkage analysis and association studies identified the Slit-Robo Rho GTPase activating protein 1 gene (SRGAP1) in the linkage peak as a candidate gene. Two missense variants, Q149H and A275T, localized in the Fes/CIP4 homology domain segregated with the disease in 1 family each. One missense variant, R617C, located in the RhoGAP domain occurred in 1 family. Biochemical assays demonstrated that the ability to inactivate CDC42, a key function of SRGAP1, was severely impaired by the Q149H and R617C variants.<bold>Conclusions: </bold>Our findings suggest that SRGAP1 is a candidate gene in PTC susceptibility. SRGAP1 is likely a low-penetrant gene, possibly of a modifier type.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2013, Vol 98, Issue 5, pE973
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2012-3823