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MEN1-Related Hyperparathyroidism: Response to Cinacalcet and Calcium-Sensing Receptor Gene Variant Arg990Gly
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2019; 40(02): 294
DOI: DOI: 10.4103/ijmpo.ijmpo_191_17
Sir,
Calcium biometabolism is usually an aberrant in abnormal parathyroid neoplasm. How blood calcium level is controlled in such cases is very interesting. The calcium-sensing receptor (CASR) plays an important role in this regard, and its polymorphism is widely studied.[1] The interrelationship between parathyroid malignancy, blood calcium, and underlying CASR polymorphism is very interesting. Whether different CASR polymorphisms have an effect on the drug treatment of the neoplasm is an important question that needs to be addressed.
An important parathyroid neoplasm with aberration of blood calcium is type 1 multiple endocrine neoplasia (MEN1). MEN1 on is usually related to primary hyperparathyroidism and has a high postsurgery recurrence rate.[2] In a recent study, Filopanti et al. reported the response to cinacalcet and its relationship with the CASR gene variant Arg990Gly.[3] Filopanti et al. mentioned no significant effect of such a polymorphism.[3] Here, the authors perform reappraisal on the effect of CASR Arg990Gly based on the quantum medicine assessment on molecular change in the polymorphism using the same technique as presented in previous publications.[4] [5] [6] It can be seen that Arg990Gly has a lower protein molecular weight than naïve type (the magnitude of decrease molecular mass per molecule is equal to 56.9%). The lower molecular mass means lower final bioaction product. This implies that MEN1 with CASR Arg990Gly should have a lower blood calcium level. If MEN1 with CASR Arg990Gly is responsive to the same dose of cinacalcet, it is likely to result in a less minimizing of blood calcium level. Of interest, this finding is concordant with the report by Filopanti et al.[3]
Publication History
Article published online:
03 June 2021
© 2019. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
Sir,
Calcium biometabolism is usually an aberrant in abnormal parathyroid neoplasm. How blood calcium level is controlled in such cases is very interesting. The calcium-sensing receptor (CASR) plays an important role in this regard, and its polymorphism is widely studied.[1] The interrelationship between parathyroid malignancy, blood calcium, and underlying CASR polymorphism is very interesting. Whether different CASR polymorphisms have an effect on the drug treatment of the neoplasm is an important question that needs to be addressed.
An important parathyroid neoplasm with aberration of blood calcium is type 1 multiple endocrine neoplasia (MEN1). MEN1 on is usually related to primary hyperparathyroidism and has a high postsurgery recurrence rate.[2] In a recent study, Filopanti et al. reported the response to cinacalcet and its relationship with the CASR gene variant Arg990Gly.[3] Filopanti et al. mentioned no significant effect of such a polymorphism.[3] Here, the authors perform reappraisal on the effect of CASR Arg990Gly based on the quantum medicine assessment on molecular change in the polymorphism using the same technique as presented in previous publications.[4] [5] [6] It can be seen that Arg990Gly has a lower protein molecular weight than naïve type (the magnitude of decrease molecular mass per molecule is equal to 56.9%). The lower molecular mass means lower final bioaction product. This implies that MEN1 with CASR Arg990Gly should have a lower blood calcium level. If MEN1 with CASR Arg990Gly is responsive to the same dose of cinacalcet, it is likely to result in a less minimizing of blood calcium level. Of interest, this finding is concordant with the report by Filopanti et al.[3]
Conflict of Interest
There are no conflicts of interest.
- Kinoshita Y. The functions of calcium-sensing receptor in regulating mineral metabolism. Clin Calcium 2017; 27: 491-7
- Giusti F, Marini F, Brandi ML. Multiple endocrine neoplasia type 1. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ. et al. editors Gene Reviews ®. Seattle (WA): University of Washington, Seattle; 1993
- Filopanti M, Verga U, Ermetici F, Olgiati L, Eller-Vainicher C, Corbetta S. et al. MEN1-related hyperparathyroidism: Response to cinacalcet and its relationship with the calcium-sensing receptor gene variant arg990Gly. Eur J Endocrinol 2012; 167: 157-64
- Joob B, Wiwanitkit V. HSD11B1 rs846908 polymorphisms and tacrolimus concentrations: Quantum chemical analysis and implication in patients with renal transplantation. J Nephropharmacol 2017; 6: 19-20
- Joob B, Wiwanitkit V. ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1) polymorphism and clopidogrel concentration in acute coronary syndrome: Molecular change can explain the observed therapeutic concentration. Anatol J Cardiol 2016; 16: 303-4
- Wiwanitkit S, Wiwanitkit V. Change in molecular weight due to important pfatp6 and pfmdr1 polymorphisms and susceptibility to antimalarial drug: Possible role of epigenetic phenomenon. Asian Pac J Trop Biomed 2017; 7: 181-2
Address for correspondence
Publication History
Article published online:
03 June 2021
© 2019. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
- Kinoshita Y. The functions of calcium-sensing receptor in regulating mineral metabolism. Clin Calcium 2017; 27: 491-7
- Giusti F, Marini F, Brandi ML. Multiple endocrine neoplasia type 1. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ. et al. editors Gene Reviews ®. Seattle (WA): University of Washington, Seattle; 1993
- Filopanti M, Verga U, Ermetici F, Olgiati L, Eller-Vainicher C, Corbetta S. et al. MEN1-related hyperparathyroidism: Response to cinacalcet and its relationship with the calcium-sensing receptor gene variant arg990Gly. Eur J Endocrinol 2012; 167: 157-64
- Joob B, Wiwanitkit V. HSD11B1 rs846908 polymorphisms and tacrolimus concentrations: Quantum chemical analysis and implication in patients with renal transplantation. J Nephropharmacol 2017; 6: 19-20
- Joob B, Wiwanitkit V. ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1) polymorphism and clopidogrel concentration in acute coronary syndrome: Molecular change can explain the observed therapeutic concentration. Anatol J Cardiol 2016; 16: 303-4
- Wiwanitkit S, Wiwanitkit V. Change in molecular weight due to important pfatp6 and pfmdr1 polymorphisms and susceptibility to antimalarial drug: Possible role of epigenetic phenomenon. Asian Pac J Trop Biomed 2017; 7: 181-2