Evidence map›Paper›PMID 30488289›Full record

Observational studyJournal of endocrinological investigation2019

GSTP1 gene methylation and AHR rs2066853 variant predict resistance to first generation somatostatin analogs in patients with acromegaly.

F Ferraù, P D Romeo, S Puglisi, M Ragonese, F Spagnolo, C Salpietro, R Ientile, M Currò, G Visalli, A Alibrandi and 2 more

Abstract readObservational Study
PubMed Publisher
In one paragraph

Observational study in Journal of endocrinological investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 19 citations in OpenAlex.

  1. DNA Methylation in Pituitary Adenomas: A Scoping Review.International journal of molecular sciences · 2025
    Article
  2. Review
  3. Novel AIP mutation in exon 6 causing acromegaly in a German family.Journal of endocrinological investigation · 2023
    Article
  4. Role of Estrogen and Estrogen Receptor in GH-Secreting Adenomas.International journal of molecular sciences · 2023
    Review
  5. Pituitary Tumorigenesis-Implications for Management.Medicina (Kaunas, Lithuania) · 2023
    Review
  6. Review
  7. Review
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

F FerraùDepartment of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy. francesco.ferrau1@gmail.com.ORCID http://orcid.org/0000-0002-7472-6598
P D RomeoDepartment of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy.
S PuglisiUnit of Endocrinology, University Hospital 'G. Martino', Messina, Italy.
M RagoneseDepartment of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy.
F SpagnoloUnit of Endocrinology, University Hospital 'G. Martino', Messina, Italy.
C SalpietroDepartment of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy.
R IentileDepartment of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, University of Messina, Messina, Italy.
M CurròDepartment of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, University of Messina, Messina, Italy.
G VisalliDepartment of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, University of Messina, Messina, Italy.
A AlibrandiDepartment of Economics, University of Messina, Messina, Italy.
I A M PicernoDepartment of Biomedical Sciences, Dental Sciences and Morpho-functional Imaging, University of Messina, Messina, Italy.
S CannavòDepartment of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy.
University of Messina · IT

Funding

Ministero della Salute (IT) RF-2013-02356201Ministero dell'Istruzione, dell'Università e della Ricerca PRIN 2015Ministero dell'Istruzione, dell'Università e della Ricerca Prot. 2015ZHKFTA
6 · The paper itself

Abstract

purposeBiomarkers of clinical and therapeutic outcome in acromegaly are needed. Polymorphisms or epigenetic changes of detoxification genes, such as those coding for the aryl hydrocarbon receptor (AHR) and the glutathione-S-transferase-P1 (GSTP1), could have a role in GH secreting pituitary tumors' pathophysiology and clinical expression. In this study, we assessed the contribution of GSTP1 gene promoter methylation status, per se or in combination with the occurrence of the AHR gene rs2066853 variant, on clinical features and response to somatostatin analogs (SSA) treatment in acromegaly patients.

methodsThis is an observational, retrospective study, carried out in the Endocrine Unit of an Italian University Hospital. We enrolled 77 wild-type AIP gene acromegaly patients, who have been screened for germline AHR rs2066853 variant and GSTP1 gene promoter methylation. Clinical and biochemical parameters were compared after patients' stratification according to GSTP1 methylation status and the presence of AHR rs2066853. We also evaluated the response to SSA treatment in 71 cases.

results17 patients carried the AHR rs2066853 variant and 26 had methylated GSTP1 (GSTP1-methyl) gene promoter. GSTP1-methyl patients showed a higher prevalence of diabetes mellitus (p = 0.01), colonic polyps (p = 0.05), and were more resistant to SSA (p = 0.02) as compared to GSTP1 unmethylated patients (GSTP1-unmethyl). Patients GSTP1-unmethyl and AHR wild-type were the most sensitive to SSA treatment, while those with both GSTP1-methyl and AHR rs2066853 variant were all resistant to SSA (p = 0.01).

conclusionsIn acromegaly, GSTP1 gene methylation associates with resistance to SSA treatment, especially in patients carrying also the AHR rs2066853 variant, and with increased prevalence of colonic polyps and diabetes mellitus.

Indexed as

Polymorphism, GeneticAcromegalyAntineoplastic Agents, HormonalBasic Helix-Loop-Helix ProteinsBiomarkersDNA MethylationDrug ResistanceFemaleFollow-Up StudiesGenotypeGlutathione S-Transferase piHumansMaleMiddle AgedOctreotidePrognosisAHR protein, humanAntineoplastic Agents, HormonalBasic Helix-Loop-Helix ProteinsBiomarkersGlutathione S-Transferase piGSTP1 protein, humanOctreotideReceptors, Aryl HydrocarbonAcromegalyAHRAHR rs2066853GSTP1GSTP1 methylationPituitary tumor

Identifiers

PMID30488289
OpenAlexW2902278035

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.