Do the aryl hydrocarbon receptor interacting protein variants (Q228K and Q307R) play a role in patients with familial and sporadic hormone-secreting pituitary adenomas?
OBJECTIVE
The aim of this study was to examine mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene by sequence analysis of exons 1-6 using leukocyte genomic DNA obtained from a cohort of familial isolated pituitary adenoma (FIPA) and apparent sporadic functional pituitary adenoma Turkish patients.


METHODS
Fourteen FIPA and 90 sporadic pituitary adenoma (somatotrophinoma, prolactinoma, and corticotrophinoma) patients, 1 sporadic gigantism case, and 70 healthy controls were included in the study.


RESULTS
We did not detect AIP mutations in patients with FIPAs or sporadic pituitary adenomas, including the gigantism case. Only two exonic homozygous missense single-nucleotide polymorphisms (rs641081 [Q228K] and rs4930195 [Q307R]) were identified in the AIP locus. Minor allele frequencies of the Q307R and Q228K variants were significantly higher in FIPA patients compared to controls. In addition, the minor allele frequency of the Q228K variant was significantly increased in patients with sporadic somatotrophinomas compared to controls, whereas the minor allele frequency of the Q307R variant was significantly increased in corticotrophinoma patients compared to controls. Conversely, the minor allele frequencies of Q228R and Q307R variants were similar between patients with prolactinomas and controls. No AIP gene mutation or variant was observed in the sporadic gigantism patient. These results suggest that Q228K and Q307R variants in the AIP gene might be involved in the genetic susceptibility to familial and sporadic pituitary adenomas (somatotrophinoma and corticotrophinoma) in the Turkish population.
1 Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University , Çapa Istanbul, Turkey .
Sema
S
Yarman
2 Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University , Çapa Istanbul, Turkey .
Yeliz Duvarci
YD
Ogret
2 Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University , Çapa Istanbul, Turkey .
Fatma Savran
FS
Oguz
D000236:Adenoma / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein