Top

Osteoporosis International

Published in:

01-08-2008 | Original Article

A C >T polymorphism located at position −1 of the Kozak sequence of CD40 gene is associated with low bone mass in Spanish postmenopausal women

Authors: B. Pineda, P. Laporta, C. Hermenegildo, A. Cano, M. A. García-Pérez

Published in: Osteoporosis International | Issue 8/2008

Abstract

Summary

This study evaluated the association of a polymorphism in the CD40 gene with BMD and risk of osteopenia or osteoporosis in a population of 602 postmenopausal women. Results showed that women with the TT genotype had lower BMD at femoral neck and spine sites and increased risk of osteopenia or osteoporosis.

Introduction

Recent findings have demonstrated that the CD40/CD40L system, which is of main importance for the immune system, can also be implied in the regulation of bone metabolism. The main objective of the present work has been to clarify whether single nucleotide polymorphisms (SNPs) affecting genes of CD40/CD40L system could be linked with abnormalities in the level of bone mineral density (BMD) in menopausal women.

Methods

We performed an association study of BMD values with a SNP located at position −1 of the Kozak consensus sequence of CD40 gene (rs1883832; C > T) in a population of 602 postmenopausal women.

Results

Women with the TT genotype (8.6% of women) displayed a reduction in femoral neck BMD (FN BMD) and lumbar spine BMD (LS BMD) of 6.2% and of 6.3%, respectively, as compared to women with CC + CT genotype. Logistic regression analysis adjusted for age, weight, and height showed that women with the TT genotype had increased risk for FN (odds ratio: 2.34; 95% CI: 1.12–4.89) and LS (odds ratio: 2.49; 95% CI: 1.19–5.24) osteopenia or osteoporosis.

Conclusions

Women with the TT genotype in rs1883832 SNP affecting to Kozak consensus sequence of CD40 gene had lower BMD at FN and at LS sites and increased risk of osteopenia or osteoporosis.

Garcia-Perez MA (2006) Physiological regulation of bone metabolism and estrogen agonism. In: Cano A, Calaf i Alsina J, Dueñas-Díez JL (eds) Selective estrogen receptor modulators: a new brand of multitarget drugs. Springer, Berlin, pp 159–184

Lacey DL, Timms E, Tan HL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176PubMedCrossRef

Kong YY, Yoshida H, Sarosi I et al (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397:315–323PubMedCrossRef

Dougall WC, Glaccum M, Charrier K et al (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13:2412–2424PubMedCrossRef

Simonet WS, Lacey DL, Dunstan CR et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319PubMedCrossRef

Yun TJ, Tallquist MD, Aicher A et al (2001) Osteoprotegerin, a crucial regulator of bone metabolism, also regulates B cell development and function. J Immunol 166:1482–1491PubMed

Roggia C, Gao Y, Cenci S et al (2001) Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo. Proc Natl Acad Sci U S A 98:13960–13965PubMedCrossRef

Cenci S, Weitzmann MN, Roggia C et al (2000) Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J Clin Invest 106:1229–1237PubMedCrossRef

Anderson DM, Maraskovsky E, Billingsley WL et al (1997) A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390:175–179PubMedCrossRef

10.

Takayanagi H, Ogasawara K, Hida S et al (2000) T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma. Nature 408:600–605PubMedCrossRef

11.

Sato T, Shibata T, Ikeda K et al (2001) Generation of bone-resorbing osteoclasts from B220+ cells: its role in accelerated osteoclastogenesis due to estrogen deficiency. J Bone Miner Res 16:2215–2221PubMedCrossRef

12.

Kanematsu M, Sato T, Takai H et al (2000) Prostaglandin E2 induces expression of receptor activator of nuclear factor-kappa B ligand/osteoprotegrin ligand on pre-B cells: implications for accelerated osteoclastogenesis in estrogen deficiency. J Bone Miner Res 15:1321–1329PubMedCrossRef

13.

Farrugia AN, Atkins GJ, To LB et al (2003) Receptor activator of nuclear factor-kappaB ligand expression by human myeloma cells mediates osteoclast formation in vitro and correlates with bone destruction in vivo. Cancer Res 63:5438–5445PubMed

14.

Li Y, Toraldo G, Li A et al (2007) B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo. Blood 109:3839–3848PubMedCrossRef

15.

Lopez-Granados E, Temmerman ST, Wu L et al (2007) Osteopenia in X-linked hyper-IgM syndrome reveals a regulatory role for CD40 ligand in osteoclastogenesis. Proc Natl Acad Sci U S A 104:5056–5061PubMedCrossRef

16.

Garcia-Perez MA, Moreno-Mercer J, Tarin JJ et al (2003) Relationship between PTH, sex steroid and bone turnover marker measurements and bone density in recently postmenopausal women. Maturitas 45:67–74PubMedCrossRef

17.

Garcia-Perez MA, Moreno-Mercer J, Tarin JJ et al (2004) Bone turnover markers and PTH levels in surgical versus natural menopause. Calcif Tissue Int 74:143–149PubMedCrossRef

18.

Kozak M (1986) Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 44:283–292PubMedCrossRef

19.

Jacobson EM, Concepcion E, Oashi T et al (2005) A Graves’ disease-associated Kozak sequence single-nucleotide polymorphism enhances the efficiency of CD40 gene translation: a case for translational pathophysiology. Endocrinology 146:2684–2691PubMedCrossRef

20.

Schrum LW, Marriott I, Butler BR et al (2003) Functional CD40 expression induced following bacterial infection of mouse and human osteoblasts. Infect Immun 71:1209–1216PubMedCrossRef

21.

Ahuja SS, Zhao S, Bellido T et al (2003) CD40 ligand blocks apoptosis induced by tumor necrosis factor alpha, glucocorticoids, and etoposide in osteoblasts and the osteocyte-like cell line murine long bone osteocyte-Y4. Endocrinology 144:1761–1769PubMedCrossRef

Title: A C >T polymorphism located at position −1 of the Kozak sequence of CD40 gene is associated with low bone mass in Spanish postmenopausal women
Authors: B. Pineda
P. Laporta
C. Hermenegildo
A. Cano
M. A. García-Pérez
Publication date: 01-08-2008
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 8/2008
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-007-0536-4

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

A C >T polymorphism located at position −1 of the Kozak sequence of CD40 gene is associated with low bone mass in Spanish postmenopausal women

Abstract

Summary

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 8/2008

NICE continues to muddy the waters of osteoporosis

Routine versus targeted vertebral fracture assessment for the detection of vertebral fractures

Effects of tibolone and raloxifene on bone mineral density in osteopenic postmenopausal women

Management of patients with Paget’s disease: a consensus document of the Belgian Bone Club

Trend of hip fracture incidence in Germany 1995–2004: a population-based study

Short-term effect of ovariectomy on osteoprogenitors in the healing rat mandibular incisor extraction socket