title: Plasma VEGF-related polymorphisms are implied in autoimmune thyroid diseases.
abstract: Autoimmune thyroid diseases (AITD), including Graves' disease (GD) and Hashimoto thyroiditis (HT), are complex multifactorial diseases. Vascular endothelial growth factor (VEGF) is implicated in various inflammatory diseases, especially autoimmune diseases. Our aim was to elucidate the relationships between plasma VEGF levels and four genome-wide association study-identified single nucleotide polymorphisms (SNPs) related to VEGF with AITD in Tunisian patients. A total of 364 healthy controls and 389 patients with AITD were genotyped for the SNPs rs6921438, rs4416670, rs6993770 and rs10738760. Levels of thyroid hormones and antibodies were quantified simultaneously with plasma VEGF after a period of six months of treatment. We found that the minor alleles of rs10738760 and rs6921438 are associated with the presence of GD. A allele of rs10738760 polymorphism is associated with increased plasma levels of free tri-iodothyronin (FT3) while no relationship was found with circulating VEGF plasma levels after six months of treatment. We also showed that the T allele of rs4416670 polymorphism was associated with increased risk of hyperthyroidism in patients treated for six months, independently of their initial diagnosis. There was no significant association between the SNPs and the risk for HT compared with controls. This study shows that AITD are influenced by 3 SNPs linked to VEGF circulating levels. Whereas rs10738760 appeared specific to GD and FT3 production after six months of treatment, rs6921438 and rs4416670 were implicated in the risk for GD. This study opens new ways to test pharmacogenomics concepts in the future especially in GD in which recurrence prognosis is still challenging.
authors.affiliation: a UMR INSERM U1122; Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Université de Lorraine , Nancy , France .|b Laboratory of Genetics, Biodiversity and Bioresource Valorization , Superior Institute of Biotechnology of Monastir, University of Monastir , Monastir , Tunisia .
authors.forename: Ines
authors.initials: I
authors.lastname: Zaaber
authors.affiliation: a UMR INSERM U1122; Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Université de Lorraine , Nancy , France .|c Department of Endocrinology , Centre Hospitalier Robert Schuman , Luxembourg , Luxembourg .
authors.forename: Marc
authors.initials: M
authors.lastname: Rancier
authors.affiliation: a UMR INSERM U1122; Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Université de Lorraine , Nancy , France .
authors.forename: Maria G
authors.initials: MG
authors.lastname: Stathopoulou
authors.affiliation: a UMR INSERM U1122; Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Université de Lorraine , Nancy , France .
authors.forename: Abdelsalam
authors.initials: A
authors.lastname: Saleh
authors.affiliation: d Department of Internal Medicine-Endocrinology , Hospital FattoumaBourguiba in Monastir , Tunisia .
authors.forename: Héla
authors.initials: H
authors.lastname: Marmouch
authors.affiliation: a UMR INSERM U1122; Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Université de Lorraine , Nancy , France .
authors.forename: Christine
authors.initials: C
authors.lastname: Masson
authors.affiliation: e Randox Laboratories Ltd , Crumlin , UK , and.
authors.forename: Helena
authors.initials: H
authors.lastname: Murray
authors.affiliation: e Randox Laboratories Ltd , Crumlin , UK , and.
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Kurth
authors.affiliation: e Randox Laboratories Ltd , Crumlin , UK , and.
authors.forename: John
authors.initials: J
authors.lastname: Lamont
authors.affiliation: e Randox Laboratories Ltd , Crumlin , UK , and.
authors.forename: Peter
authors.initials: P
authors.lastname: Fitzgerald
authors.affiliation: d Department of Internal Medicine-Endocrinology , Hospital FattoumaBourguiba in Monastir , Tunisia .
authors.forename: Selvia
authors.initials: S
authors.lastname: Mahjoub
authors.affiliation: b Laboratory of Genetics, Biodiversity and Bioresource Valorization , Superior Institute of Biotechnology of Monastir, University of Monastir , Monastir , Tunisia .
authors.forename: Khaled
authors.initials: K
authors.lastname: Said
authors.affiliation: b Laboratory of Genetics, Biodiversity and Bioresource Valorization , Superior Institute of Biotechnology of Monastir, University of Monastir , Monastir , Tunisia .
authors.forename: Besma
authors.initials: B
authors.lastname: Bel Hadj Jrad Tensaout
authors.affiliation: b Laboratory of Genetics, Biodiversity and Bioresource Valorization , Superior Institute of Biotechnology of Monastir, University of Monastir , Monastir , Tunisia .
authors.forename: Souhir
authors.initials: S
authors.lastname: Mestiri
authors.affiliation: a UMR INSERM U1122; Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Université de Lorraine , Nancy , France .|f Department of Internal Medicine and Geriatrics , CHU Nancy-Brabois , France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Visvikis-Siest
mesh_terms: D000483:Alleles; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006111:Graves Disease / Q000097:blood / Q000235:genetics; D050031:Hashimoto Disease / Q000097:blood / Q000235:genetics; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013959:Thyroid Diseases / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D042442:Vascular Endothelial Growth Factors / Q000097:blood* / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D042442:Vascular Endothelial Growth Factors
keywords: Genetics; Graves’ disease; Hashimoto thyroiditis; VEGF; polymorphisms