Endocrine Abstracts (2017) 49 EP232 | DOI: 10.1530/endoabs.49.EP232

May serotonin metabolism polymorphisms 5HTTVNTR and 5HT2A have a clinical impact in osteoporosis development?

Raquel Simões1,2, Joana Freitas1,2, Ana Paula Barbosa3,4, Rui Mascarenhas3,4 & Manuel Bicho1,2

1Institute for Scientific Research Bento Rocha Cabral, Lisbon, Portugal; 2ISAMB, Genetics Laboratory, Lisbon Medical School, Lisbon, Portugal; 3Clinic of Endocrinology, Diabetes and Metabolism, Lda., Lisbon, Portugal; 4Department of Endocrinology, Diabetes and Metabolism, Santa Maria Hospital, Lisbon, Portugal.

Objectives: To study the association of serotonin transporter gene (SLC6A4) polymorphism 5HTTVNTR and serotonin receptor 2A polymorphism 5HT2A_T102C with bone mineral density and metabolic parameters of bone remodelling.

Materials and methods: BMD (g/cm2) was measured by DEXA in 105 post-menopausal women: 35 with normal BMD (age=58.30±1.33 years; BMI=28.18 [19.13-39.87] kg/m2) and 70 with osteoporosis (age=68.30±1.09 years; BMI=28.90 [20.78-43.86] kg/m2). Metabolic bone remodelling parameters were analysed: LDL, HDL, total cholesterol, HOMAIR, insulin, glycaemia, alkaline phosphatase, osteocalcin and parathormone. It was determined the platelet and plasma serotonin concentrations by ELISA. 5HTTVNTR was evaluated by PCR and the 5HT2A_T102C by PCR-RFLP. Statistical analysis by SPSS 21.0.

Results: In osteoporosis, we found increased osteocalcin (P=0.030) and plasma 5HT concentration (P=0.012) and decreased insulin (P=0.023) and total cholesterol (P=0.027). In women with normal BMD, we found an association between genotype 10/10 of 5HTTVNTR and decreased osteocalcin (P=0.035). and between genotype CC of 5HT2A and decreased HDL (P=0.029). Within this group, we also found inverse correlations between HDL and alkaline phosphatase (P=0.030) and HOMAIR (P=0.018). In women with osteoporosis, we found direct correlations between glycaemia and osteocalcin (P=0.017) and HDL (P=0.049).

Conclusion: In normal BMD, 5HTTVNTR and 5HT2A_T102C polymorphisms appear to modulate directly or indirectly some metabolic parameters associated with bone remodelling. These polymorphisms seem to have no effect in women with osteoporosis suggesting that they may play a relevant role in the susceptibility to osteoporosis development by modulating metabolic bone remodelling parameters.

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