title: The C allele of the GNB3 C825T polymorphism of the G protein beta3-subunit is associated with an increased risk for the development of oncocytic thyroid tumours.
abstract: Carriers of the C allele of the common C825T polymorphism in the GNB3 gene of the G protein have been associated with the development of follicular thyroid adenomas. Since the C allele of this polymorphism is related to a lower signalling capacity, it was speculated whether the C825T polymorphism may play a particular role in oncocytic thyroid tumours, which are recognized for their reduced ability to synthesize thyroid-specific proteins and hormones, although they possess an intact thyroid-stimulating hormone receptor-adenylyl cyclase system. Using pyrosequencing, both the genotype distribution and the allele frequency of the C825T polymorphism were investigated in a series of 104 patients with oncocytic thyroid tumours of follicular cell origin [58 adenomas, 41 follicular thyroid carcinomas (FTCs), and five papillary thyroid carcinomas (PTCs)]; the results were compared with those obtained from 321 age and gender-matched healthy blood donors and a series of 327 non-oncocytic thyroid tumours of follicular cell origin (119 adenomas, 80 FTCs, and 186 PTCs). Analysis of the genotype distribution (comparing oncocytic with non-oncocytic tumours of the present series) revealed a significantly increased odds ratio (OR) for CC versus TT (OR = 4.22; p = 0.011) and CC versus CT (OR = 1.62; p = 0.049) carriers to develop an oncocytic thyroid tumour; ORs to develop an oncocytic thyroid tumour were also increased comparing the genotype distribution between the group of oncocytic tumours and healthy controls for CC versus TT (OR = 3.73; p = 0.017) and CC versus all T carriers (OR = 1.56; p = 0.034). Oncocytic thyroid tumours as a group showed a statistically significant increase of the C-allele frequency when compared with all non-oncocytic tumours (p = 0.0039) as well as healthy blood donors (p = 0.017). The results strongly suggest that the C allele of the GNB3 C825T polymorphism of the G protein beta3-subunit is associated with an increased risk for the development of oncocytic thyroid tumours. This polymorphism may thus be considered a (co)factor favouring the development of oncocytic thyroid tumours, although the biological mechanism(s) underlying this association remain obscure.
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital of Essen, Germany.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Sheu
authors.forename: S
authors.initials: S
authors.lastname: Handke
authors.forename: M
authors.initials: M
authors.lastname: Bröcker-Preuss
authors.forename: R
authors.initials: R
authors.lastname: Görges
authors.forename: U H
authors.initials: UH
authors.lastname: Frey
authors.forename: C
authors.initials: C
authors.lastname: Ensinger
authors.forename: D
authors.initials: D
authors.lastname: Ofner
authors.forename: N R
authors.initials: NR
authors.lastname: Farid
authors.forename: W
authors.initials: W
authors.lastname: Siffert
authors.forename: K W
authors.initials: KW
authors.lastname: Schmid
mesh_terms: D000236:Adenoma / Q000235:genetics; D018249:Adenoma, Oxyphilic / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002291:Carcinoma, Papillary / Q000235:genetics; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D013963:Thyroid Hormones / Q000096:biosynthesis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: C454420:G-protein beta3 subunit; D013963:Thyroid Hormones; D020962:Heterotrimeric GTP-Binding Proteins