Common polymorphisms in GHRd3, IGFBP3 and IGF1 genes do not explain GH-IGF-I dissociation in treated acromegalic patients

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 109-133-GHRH, GH & IGF Biology & Signaling
Bench to Bedside
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-129
Daniel Ossamu Goldschmidt Kiminami*1, Paula CL Elias1, Fernanda Borchers Coeli-Lacchini2, Silvia Ruiz Roa1, Margaret De Castro2, Sonir Roberto Antonini2 and Ayrton Custodio Moreira2
1School of Medicine of Ribeirao Preto- University of Sao Paulo, Ribeirao Preto SP, Brazil, 2School of Medicine of Ribeirao Preto-University of Sao Paulo, Ribeirao Preto-SP, Brazil
Context: Biochemical criteria for acromegaly remission have become stricter with plasma IGF-I and GH highly sensitive assays. Based on the last consensus, a subgroup of post-treatment acromegalic patients with GH-IGF-I dissociation (GH criteria of remission with IGF-I levels above normal range) has been described. Three different polymorphisms in the GH-IGF-I axis (GHRd3, -202 A/C IGFBP3 and 737.738 IGF1) have been linked to IGF1 and/or IGFBP3 levels and response to GH treatment. The interactive involvement of these 3 polymorphisms in acromegaly phenotype and in GH-IGF-I dissociation has not been evaluated.

Objective: To evaluate the individual and combined influence of these polymorphisms in plasma IGF-I and IGFBP3 concentrations in acromegaly, their relationship with type 2 diabetes (T2DM), high blood pressure (HBP), obesity, and their possible role in the mechanism of GH-IGF-I dissociation.

Subjects and methods: IGF-I and IGFBP3 levels as well as DNA genotype for all three polymorphisms were analyzed in 221 normal controls and in 68 post-treatment acromegalic patients, including 12 patients with GH-IGF-1 dissociation. In the acromegalic group, GH-IGF-I levels and comorbidities at the time of diagnosis (T2DM, HBP, obesity), and biochemical follow-up were obtained. The GHRd3 and the -202A/C polymorphisms were analyzed using the either recessive or codominant model. For the 737.738 IGF-1 we assumed 19CA isolated or combined with the 20CA as Wild Types.

Results: A positive correlation was found between IGF-I and IGFBP3 levels in controls and in acromegalic patients (r=0.14 and r=0.32; P<0.0001). Higher IGFBP3 levels were found in AA-202A/C subjects than in CC genotype in both acromegalic (80±4.6 vs 66±4.3 µg/mL; P<0.05) and control group (64±2 vs 58±2 µg/mL; P<0.03). No association was found between the IGFBP3 levels and the other two polymorphisms, isolated or in conjunction, even when combined with the -202A/C. The individual and combined analysis of the GHRd3, the 737.738 IGF1 and the -202A/C polymorphisms showed no association with IGF-I levels, acromegaly comorbidities, or with GH- IGF-I dissociation in treated acromegalic patients.

Conclusion: In acromegalic patients, GHRd3, -202A/C IGFBP3 and 737.738 IGF1 polymorphisms were not associated with IGF-I levels neither with the prevalence of comorbidities. In addition, these polymorphisms do not explain the GH-IGF-I dissociation observed in a subgroup of treated acromegalic patients.

Nothing to Disclose: DOGK, PCE, FBC, SRR, MD, SRA, ACM

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: FAPESP Grants # 2010/19454-3; 07/58365-3 CNPQ # 314279/2009-1