Startseite
English
Erweiterte Suche
Durchblättern nach ...
Publikationen im Überblick
Ansprechpartner
Hilfe
DOI
PMC
 |
|
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Association between the p27 rs2066827 variant and tumor multiplicity in patients harboring MEN1 germline mutations.
Eur. J. Endocrinol. 171, 335-342 (2014)
Objetive: To date, no evidence of robust genotype-phenotype correlation or disease modifiers for Multiple endocrine neoplasia type 1 (MEN1) syndrome have been described, leaving the highly variable clinical presentation of the patients unaccounted for. Design: Because the CDKN1B (p27) gene causes MEN4 syndrome and it is transcriptionally regulated by the product of the MEN1 gene (Menin), we sought to analyze whether p27 influences the phenotype of MEN1-mutated patients. The cohort consisted of one hundred patients carrying germline MEN1 gene mutations and 855 population-matched control individuals. Methods: Genotyping of the coding p27 c.326T>G (V109G) variant was performed by sequencing and restriction site digestion, and the genotypes were associated with clinical parameters by calculating odds ratios (ORs) and their 95% confidence intervals (CIs) using logistic regression. Results: There were significant differences in p27 V109G allele frequencies between controls and MEN1-mutated patients (OR= 2.55, p= 0.019, C.I.= 1.013-5.76). Among patients ≥30 y old carrying truncating MEN1 mutations, the T allele was strongly associated with susceptibility to tumors in multiple glands (3-4 glands affected vs. 1-2 glands affected; OR=18.33; p=0.002, C.I.=2.88-16.41). This finding remained significant after Bonferroni multiple testing correction, indicating a robust association. No correlations were observed with the development of MEN1-related tumors such as hyperparathyroidism, pituitary adenomas, enteropancreatic and adrenocortical tumors. Conclusions: Our study suggests that the p27 tumor suppressor gene acts as a disease modifier for the MEN1 syndrome associated with MEN1 germline mutations. If confirmed in independent patient cohorts, this finding could facilitate the management of this clinically complex disease.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Endocrine-neoplasia Type-1; V109g Polymorphism; Primary Hyperparathyroidism; Clinical Expression; Gene; P27(kip1); Mice; Cdkn1b; Identification; Tumorigenesis
ISSN (print) / ISBN
0804-4643
e-ISSN
1479-683X
Zeitschrift
European Journal of Endocrinology
Quellenangaben
Band: 171,
Heft: 3,
Seiten: 335-342
Verlag
BioScientifica
Verlagsort
Bristol
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pathology (PATH)