Skip to main content
Log in

Malic enzyme gene polymorphism is associated with responsiveness in circulating parathyroid hormone after long-term calcium supplementation

  • Malic Enzyme Gene Polymorphism
  • Published:
The journal of nutrition, health & aging

Abstract

Objective

To identify genetic variations associated with parathyroid hormone (PTH) suppression after long-term calcium supplementation.

Design and Participants

For high throughput SNP screening, subjects consisted of 171 postmenopausal women without osteoporosis at the lumbar spine. A separate group of 19 premenpausal women were recruited for calcium absorption study. Postmenopausal women in the screening group were given 500 mg/day calcium supplementation.

Setting

Bangkok, Thailand.

Measurements

Parathyroid hormone (PTH) and bone mineral density (BMD) were measured at baseline and 2 years after calcium supplementation. High throughput single-nucleotide polymorphism (SNP) screening was performed by comparing estimated allele frequencies derived from hybridization signal intensities of pooled DNA samples on Affymetrix’s 10K SNP genotyping microarrays based responsiveness in PTH after calcium supplementation. Genotyping of SNP rs1112482 in malic enzyme gene (ME1) gene, a SNP among those with highest odds ratio of being related to PTH suppression after calcium, was performed in all postmenopausal subjects in the screening group and premenopausal women in the calcium absorption study group in which fractional calcium absorption was assessed by stable isotope dilution. Data were expressed as mean +/− SEM.

Results

PTH significantly decreased after 2 years of calcium supplementation (4.7 + 1.9 vs. 4.4 + 1.6 pmol/L, P < 0.01). There was a significant increase in lumbar spine BMD (1.03 + 0.01 vs. 1.01 + 0.01 g/cm2, P < 0.001) but not femoral neck BMD. In 108 subjects whose PTH levels decreased after calcium, the suppression of PTH was higher in those with at least one C allele in rs1112482 of ME1 gene (−26.3 + 2.1 vs. −16.9 + 1.4%, P < 0.001). Fractional calcium absorption also tends to the higher in subjects in the calcium absorption study group with at least one C allele (n = 6) compared to those without the C allele (n = 13) (58.0 + 4.9 vs. 49.3 + 2.8%, P = 0.054).

Conclusion

Cytosolic malic enzyme 1 gene polymorphism is associated with the degree of suppression of parathyroid hormone after long-term calcium supplementation. The effect is probably mediated through an increase in intestinal calcium absorption.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Lei SF, Jiang H, Deng FY, Deng HW. Searching for genes underlying susceptibility to osteoporotic fracture: current progress and future prospect. Osteoporos Int 2007;18:1157–1175.

    Article  PubMed  Google Scholar 

  2. Usui T, Urano T, Shiraki M, Ouchi Y, Inoue S. Association of a single nucleotide polymorphism in Wnt10bgene with bone mineral density. Geriatr Gerontol Int 2007;7:48–53.

    Article  Google Scholar 

  3. Fang Y, Rivadeneira F, van Meurs JB, Pols HA, Ioannidis JP, Uitterlinden AG. Vitamin D receptor gene BsmI and TaqI polymorphisms and fracture risk: a metaanalysis. Bone 2006;39:938–945.

    Article  PubMed  CAS  Google Scholar 

  4. Mann V, Ralston SH. Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone 2003;32:711–717.

    Article  PubMed  CAS  Google Scholar 

  5. Wang CL, Tang XY, Chen WQ, Su YX, Zhang CX, Chen YM. Association of estrogen receptor alpha gene polymorphisms with bone mineral density in Chinese women: a meta-analysis. Osteoporos Int 2007;18:295–305.

    Article  PubMed  Google Scholar 

  6. Aloia JF, Arunabh-Talwar S, Pollack S, Yeh JK. The remodeling transient and the calcium economy. Osteoporos Int 2008;19:1001–1009.

    Article  PubMed  CAS  Google Scholar 

  7. Heaney RP. The bone-remodeling transient: implications for the interpretation of clinical studies of bone mass change. J Bone Miner Res 1994;9:1515–1523.

    Article  PubMed  CAS  Google Scholar 

  8. Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007;370:657–666.

    Article  PubMed  CAS  Google Scholar 

  9. Fleet JC, Harris SS, Wood RJ, Dawson-Hughes B. The BsmI vitamin D receptor restriction fragment length polymorphism (BB) predicts low bone density in premenopausal black and white women. J Bone Miner Res 1995;10:985–990.

    Article  PubMed  CAS  Google Scholar 

  10. Matsuzaki H, Loi H, Dong S, Tsai YY, Fang J, Law J, Di X, Liu WM, Yang G, Liu G, Huang J, Kennedy GC, Ryder TB, Marcus GA, Walsh PS, Shriver MD, Puck JM, Jones KW, Mei R. Parallel genotyping of over 10,000 SNPs using a one-primer assay on a high-density oligonucleotide array. Genome Res 2004;14:414–425.

    Article  PubMed  CAS  Google Scholar 

  11. Simpson CL, Knight J, Butcher LM, Hansen VK, Meaburn E, Schalkwyk LC, Craig IW, Powell JF, Sham PC, Al-Chalabi A. A central resource for accurate allele frequency estimation from pooled DNA genotyped on DNA microarrays. Nucleic Acids Res 2005;33:e25.

    Article  PubMed  Google Scholar 

  12. Butcher LM, Meaburn E, Liu L, Fernandes C, Hill L, Al-Chalabi A, Plomin R, Schalkwyk L, Craig IW. Genotyping pooled DNA on microarrays: a systematic genome screen of thousands of SNPs in large samples to detect QTLs for complex traits. Behav Genet 2004;34:549–555.

    Article  PubMed  Google Scholar 

  13. Charoenkiatkul S, Kriengsinyos W, Tuntipopipat S, Suthutvoravut U, Weaver CM. Calcium absorption from commonly consumed vegetables in healthy Thai women. J Food Sci 2008;73:H218–221.

    Article  PubMed  CAS  Google Scholar 

  14. Zhao Y, Martin BR, Weaver CM. Calcium bioavailability of calcium carbonate fortified soymilk is equivalent to cow’s milk in young women. J Nutr 2005;135:2379–2382.

    PubMed  CAS  Google Scholar 

  15. Heaney RP, Recker RR. Estimation of true calcium absorption. Ann Intern Med 1985;103:516–521.

    PubMed  CAS  Google Scholar 

  16. Heaney RP, Recker RR. Estimating true fractional calcium absorption. Ann Intern Med 1988;108:905–906.

    PubMed  CAS  Google Scholar 

  17. Singh R, Lemire J, Mailloux RJ, Appanna VD. A novel strategy involved antioxidative defense: the conversion of NADH into NADPH by a metabolic network. PLoS ONE 2008;3:e2682.

    Article  PubMed  Google Scholar 

  18. Marchionatti AM, Perez AV, Diaz de Barboza GE, Pereira BM, Tolosa de Talamoni NG. Mitochondrial dysfunction is responsible for the intestinal calcium absorption inhibition induced by menadione. Biochim Biophys Acta 2008;1780:101–107.

    Article  PubMed  CAS  Google Scholar 

  19. Seeman E, Compston J, Adachi J, Brandi ML, Cooper C, Dawson-Hughes B, Jonsson B, Pols H, Cramer JA. Non-compliance: the Achilles’ heel of anti-fracture efficacy. Osteoporos Int 2007;18:711–719.

    Article  PubMed  CAS  Google Scholar 

  20. Cooper A, Drake J, Brankin E. Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study. Int J Clin Pract 2006;60:896–905.

    Article  PubMed  CAS  Google Scholar 

  21. Guilera M, Fuentes M, Grifols M, Ferrer J, Badia X. Does an educational leaflet improve self-reported adherence to therapy in osteoporosis? The OPTIMA study. Osteoporos Int 2006;17:664–671.

    Article  PubMed  CAS  Google Scholar 

  22. Delmas PD, Vrijens B, Eastell R, Roux C, Pols HA, Ringe JD, Grauer A, Cahall D, Watts NB. Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 2007;92:1296–1304.

    Article  PubMed  CAS  Google Scholar 

  23. Matkovic V, Kostial K, Simonovic I, Buzina R, Brodarec A, Nordin BE. Bone status and fracture rates in two regions of Yugoslavia. Am J Clin Nutr 1979;32:540–549.

    PubMed  CAS  Google Scholar 

  24. Chevalley T, Rizzoli R, Nydegger V, Slosman D, Rapin CH, Michel JP, Vasey H, Bonjour JP. Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin-D-replete elderly patients. Osteoporos Int 1994;4:245–252.

    Article  PubMed  CAS  Google Scholar 

  25. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997;337:670–676.

    Article  PubMed  CAS  Google Scholar 

  26. Dvorak MM, Siddiqua A, Ward DT, Carter DH, Dallas SL, Nemeth EF, Riccardi D. Physiological changes in extracellular calcium concentration directly control osteoblast function in the absence of calciotropic hormones. Proc Natl Acad Sci U S A 2004;101:5140–5145.

    Article  PubMed  CAS  Google Scholar 

  27. Ahlstrom M, Pekkinen M, Riehle U, Lamberg-Allardt C. Extracellular calcium regulates parathyroid hormone-related peptide expression in osteoblasts and osteoblast progenitor cells. Bone 2008;42:483–490.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to La-or Chailurkit.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chailurkit, Lo., Chanprasertyothin, S., Charoenkiatkul, S. et al. Malic enzyme gene polymorphism is associated with responsiveness in circulating parathyroid hormone after long-term calcium supplementation. J Nutr Health Aging 16, 246–251 (2012). https://doi.org/10.1007/s12603-011-0343-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12603-011-0343-7

Key words

Navigation