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Gene–gene interaction between CD40 and CD40L reduces bone mineral density and increases osteoporosis risk in women

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Abstract

Summary

We have analysed the association of single-nucleotide polymorphisms (SNPs) in CD40 and CD40L genes with bone mineral density (BMD) in our women. Results showed that women with TT genotype for rs1883832 (CD40) and for rs1126535 (CD40L) SNPs displayed reduced BMD and increased risk for osteopenia/osteoporosis. Our data notwithstanding, the results need to be replicated.

Introduction

Recent data have revealed that the CD40/CD40L system can be implicated in bone metabolism regulation. Moreover, we previously demonstrated that rs1883832 in the CD40 gene was significantly associated with BMD and osteoporosis risk. The objective of the present work was to determine whether polymorphisms in CD40 and CD40L genes are associated with BMD and osteoporosis risk.

Methods

We conducted an association study of BMD values with SNPs in CD40 and CD40L genes in a population of 811 women of which 693 and 711 had femoral neck (FN) and lumbar spine (LS) densitometric studies, respectively.

Results

Women with the TT genotype for rs1883832 (CD40) showed a reduction in FN-BMD (P = 0.005) and LS-BMD (P = 0.020) when compared with women with the CC/CT genotype. Moreover, we found that rs1126535 (CD40L) was significantly associated with LS-BMD so that women with the TT genotype displayed lower BMD (P = 0.014) than did women with the CC/CT genotype. Interestingly, we have found a strong interaction between polymorphisms in these genes. Thus, women with the TT genotype for both rs1883832 and rs1126535 SNPs (TT + TT women) showed a lower age-adjusted BMD (Z-score) for FN (P = 0.0007) and LS (0.007) after adjusting by years since menopause, body mass index, smoking and menopausal status, densitometer type, hormone replacement therapy (HRT) use and HRT duration and after making the Bonferroni adjustment for multiple comparisons than did the remaining women. Logistic regression analysis adjusted by these covariates showed that TT + TT women had increased risk for FN (odds ratio (OR) = 2.76; P = 0.006) and LS (OR = 2.39; P = 0.020) osteopenia or osteoporosis than did the other women.

Conclusions

Our results suggest that interaction between genetic variants in the CD40 and CD40L genes exerts a role on BMD regulation. Further studies, which we welcome, are needed to replicate these data in other populations.

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Acknowledgments

The authors are indebted to Mrs. R. Aliaga and Mrs. E. Calap for their excellent technical assistance. MAG-P is a recipient of a research contract from Fondo de Investigación Sanitaria-Consellería de Sanitat (Generalitat Valenciana).

Grants

This work was supported by grants PI06/154 and PS09/00184 from Fondo de Investigación Sanitaria (FIS, Madrid, Spain), AP-024/07, EVES 045-2007 and AP-077/08 from Conselleria de Sanitat (Generalitat Valenciana), Red HERACLES RD06/0009/0005 from Instituto Carlos III (Ministerio de Ciencia e Innovación; Madrid, Spain) and Fundación Santiago Dexeus Font (Barcelona, Spain).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Research Foundation, Hospital Clínico Universitario, Av. Blasco Ibáñez, 17, 46010, Valencia, Spain

    B. Pineda & M. Á. García-Pérez

  2. Department of Functional Biology and Physical Anthropology, University of Valencia, Valencia, Spain

    J. J. Tarín

  3. Department of Physiology, University of Valencia, Valencia, Spain

    C. Hermenegildo

  4. Clinical Biochemistry Service, Hospital Clínico Universitario, Valencia, Spain

    P. Laporta

  5. Department of Paediatrics, Obstetrics and Gynaecology, University of Valencia, Valencia, Spain

    A. Cano

  6. Department of Genetics, University of Valencia, Valencia, Spain

    M. Á. García-Pérez

Authors
  1. B. Pineda
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  2. J. J. Tarín
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  3. C. Hermenegildo
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  4. P. Laporta
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  5. A. Cano
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  6. M. Á. García-Pérez
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Corresponding author

Correspondence to M. Á. García-Pérez.

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Pineda, B., Tarín, J.J., Hermenegildo, C. et al. Gene–gene interaction between CD40 and CD40L reduces bone mineral density and increases osteoporosis risk in women. Osteoporos Int 22, 1451–1458 (2011). https://doi.org/10.1007/s00198-010-1324-0

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  • DOI: https://doi.org/10.1007/s00198-010-1324-0

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