Skip to main content
Erschienen in: Osteoporosis International 8/2008

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

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

Erschienen in: Osteoporosis International | Ausgabe 8/2008

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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 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
2.
Zurück zum Zitat Lacey DL, Timms E, Tan HL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176PubMedCrossRef Lacey DL, Timms E, Tan HL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176PubMedCrossRef
3.
Zurück zum Zitat 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 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
4.
Zurück zum Zitat Dougall WC, Glaccum M, Charrier K et al (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13:2412–2424PubMedCrossRef Dougall WC, Glaccum M, Charrier K et al (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13:2412–2424PubMedCrossRef
5.
Zurück zum Zitat 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 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
6.
Zurück zum Zitat 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 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
7.
Zurück zum Zitat 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 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
8.
Zurück zum Zitat 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 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
9.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Kozak M (1986) Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 44:283–292PubMedCrossRef Kozak M (1986) Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 44:283–292PubMedCrossRef
19.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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
Metadaten
Titel
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
verfasst von
B. Pineda
P. Laporta
C. Hermenegildo
A. Cano
M. A. García-Pérez
Publikationsdatum
01.08.2008
Verlag
Springer-Verlag
Erschienen in
Osteoporosis International / Ausgabe 8/2008
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-007-0536-4

Weitere Artikel der Ausgabe 8/2008

Osteoporosis International 8/2008 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.