title: Polymorphisms in MEN1 and DRD2 genes are associated with the occurrence and characteristics of pituitary adenomas.
abstract: OBJECTIVE
  Although pituitary adenomas (PAs) affect a significant proportion of the population, only a fraction have the potential to become clinically relevant during an individual's lifetime, causing hormonal imbalance or complications due to mass effect. The overwhelming majority of cases are sporadic and without a clear familial history, and the genotype-phenotype correlation in PA patients is poorly understood. Our aim was to investigate the involvement of genes known for their role in familial cases on drug response and tumor suppression in the development and pathology of PAs in a patient group from Latvia.
  
  
  METHODS
  The study included 143 cases and 354 controls, we investigated the role of single-nucleotide polymorphisms (SNPs) in seven genes (SSTR2, SSTR5, DRD2, MEN1, AIP, GNAS, and PRKAR1A) associated with pituitary tumor occurrence, phenotype, and clinical symptoms.
  
  
  METHODS
  Genotyping of 96 tag and nonsynonymous SNPs was performed in the genomic regions of interest.
  
  
  RESULTS
  We discovered a significant association (OR=17.8, CI 0.95=2.18-145.5, P=0.0002) between a rare MEN1 mutation (rs2959656) and clinically active adenoma in our patients. Additionally, rs7131056 at DRD2 was associated with a higher occurrence of extrasellar growth in patients with prolactinoma and somatotropinoma (OR=2.79, CI 0.95=1.58-4.95, P=0.0004).
  
  
  CONCLUSIONS
  rs2959656, a nonsynonymous variant in MEN1, is associated with the development of clinically active PA. Furthermore, rs7131056 in DRD2 contributes to either faster growth of the adenoma or reduced symptomatic presentation, allowing PAs to become larger before detection.
authors.affiliation: Latvian Biomedical Research and Study CentreRiga, Latvia.
authors.forename: Raitis
authors.initials: R
authors.lastname: Peculis
authors.affiliation: Pauls Stradiņš Clinical University HospitalRiga, Latvia Faculty of MedicineUniversity of Latvia, Riga, Latvia.
authors.forename: Inga
authors.initials: I
authors.lastname: Balcere
authors.affiliation: Latvian Biomedical Research and Study CentreRiga, Latvia.
authors.forename: Vita
authors.initials: V
authors.lastname: Rovite
authors.affiliation: Latvian Biomedical Research and Study CentreRiga, Latvia.
authors.forename: Kaspars
authors.initials: K
authors.lastname: Megnis
authors.affiliation: Riga Eastern Clinical University HospitalRiga, Latvia.
authors.forename: Andra
authors.initials: A
authors.lastname: Valtere
authors.affiliation: Pauls Stradiņš Clinical University HospitalRiga, Latvia.
authors.forename: Janis
authors.initials: J
authors.lastname: Stukens
authors.affiliation: Riga Eastern Clinical University HospitalRiga, Latvia.
authors.forename: Ligita
authors.initials: L
authors.lastname: Arnicane
authors.affiliation: Latvian Biomedical Research and Study CentreRiga, Latvia.
authors.forename: Liene
authors.initials: L
authors.lastname: Nikitina-Zake
authors.affiliation: Riga Eastern Clinical University HospitalRiga, Latvia.
authors.forename: Aivars
authors.initials: A
authors.lastname: Lejnieks
authors.affiliation: Latvian Biomedical Research and Study CentreRiga, Latvia Pauls Stradiņš Clinical University HospitalRiga, Latvia Faculty of MedicineUniversity of Latvia, Riga, Latvia.
authors.forename: Valdis
authors.initials: V
authors.lastname: Pirags
authors.affiliation: Latvian Biomedical Research and Study CentreRiga, Latvia klovins@biomed.lu.lv.
authors.forename: Janis
authors.initials: J
authors.lastname: Klovins
mesh_terms: D000236:Adenoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D000328:Adult; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010911:Pituitary Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*
chemical_list: C581293:DRD2 protein, human; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D017448:Receptors, Dopamine D2