Raitis Peculis1, Inga Balcere2, Vita Rovite1, Kaspars Megnis1, Andra Valtere3, Janis Stukens4, Ligita Arnicane3, Liene Nikitina-Zake1, Aivars Lejnieks3, Valdis Pirags5, Janis Klovins6. 1. Latvian Biomedical Research and Study CentreRiga, Latvia. 2. Pauls Stradiņš Clinical University HospitalRiga, Latvia Faculty of MedicineUniversity of Latvia, Riga, Latvia. 3. Riga Eastern Clinical University HospitalRiga, Latvia. 4. Pauls Stradiņš Clinical University HospitalRiga, Latvia. 5. Latvian Biomedical Research and Study CentreRiga, Latvia Pauls Stradiņš Clinical University HospitalRiga, Latvia Faculty of MedicineUniversity of Latvia, Riga, Latvia. 6. Latvian Biomedical Research and Study CentreRiga, Latvia klovins@biomed.lu.lv.
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. DESIGN: 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.
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. DESIGN: 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.