Abstract
The present study investigated the interaction between Cdx-2 polymorphism and physical activity level over bone mineral density (BMD) variation in Brazilian postmenopausal women. One hundred and ninety women volunteered to participate in the study (66.6 ± 5.3 years, 64.58 ± 11.74 kg and 151.94 ± 6.36 cm). Physical activity level (PAL) was assessed using the international physical activity questionnaire (IPAQ). Lumbar spine (L2 - L4), femoral neck, great trochanter and Wards' triangle bone mineral density (BMD) were measured by dual-energy X‐ray absorptiometry (DXA). The Cdx-2 polymorphism was genotyped by minisequencing, using the SNaPshot™ Multiplex System (Applied Biosystems, Foster City, CA, USA). Overall, no significant association was found between Cdx-2 polymorphism and adjusted BMD at any site. However, the results revealed a significant interaction between PAL and Cdx-2 genotype on adjusted femoral neck and Wards' triangle BMD. Active women carrying the Cdx-G/G genotype showed higher adjusted femoral neck and Wards' triangle BMD than inactive women carrying the same genotype, thus suggesting a larger chronic response to physical activity. These results suggest that, in postmenopausal women, the Cdx-2 polymorphism does not influence BMD by itself; however, it seems to affect the BMD response to physical activity since only the Cdx-G/G genotype carriers presented significant differences between active and inactive.
Key words
vitamin D receptor - osteoporosis - genetics - minisequencing
References
-
1
Abrams S A, Griffin I J, Hawthorne K M, Chen Z, Gunn S K, Wilde M, Darlington G, Shypailo R J, Ellis K J.
Vitamin D receptor Fok1 polymorphisms affect calcium absorption, kinetics and bone mineralization rates during puberty.
J Bone Miner Res.
2005;
20
945-953
-
2
Ames S K, Ellis K J, Gunn S K, Copeland K C, Abrams S A.
Vitamin D receptor gene FokI polymorphism predicts calcium absorption and bone mineral density in children.
J Bone Miner Res.
1999;
14
740-746
-
3
Amling M, Priemel M, Holzmann T, Chapin K, Rueger Jm, Baron R, Demay M B.
Rescue of the skeletal phenotype of vitamin D receptor ablated mice in the setting of normal mineral ion homeostasis: formal histomorphometric and biomechanical analyses.
Endocrinology.
1999;
140
4982-4987
-
4
Arai H, Miyamoto K, Yoshida M, Yamamoto H, Taketani Y, Morita K, Kubota M, Yoshida S, Ikeda M, Watabe F, Kanemasa Y, Takeda E.
The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene.
J Bone Miner Res.
2001;
16
1256-1264
-
5
Block J E.
Interpreting studies of exercise and osteoporosis: a call for rigor.
Control Clin Trials.
1997;
18
54-57
-
6
Bray M S.
Genomics, genes, and environmental interaction: the role of exercise.
J Appl Physiol.
2000;
88
787-792
-
7
Coupland C A, Cliffe S J, Bassey E J, Grainge M J, Hosking D J, Chilvers C E.
Habitual physical activity and bone mineral density in postmenopausal women in England.
Int J Epidemiol.
1999;
28
241-246
-
8
Cummings S R.
Risk factors for hip fractures in white women.
N Engl J Med.
1995;
332
767-773
-
9
Deng H W, Livshits G, Yakovenko K, Xu F H, Conway T, Davies K M, Deng H, Recker R R.
Evidence for a major gene for bone mineral density/content in human pedigrees identified via probands with extreme bone mineral density.
Ann Hum Genet.
2002;
66
61-74
-
10
Dequecker J, Nijs J, Verstraeten A, Geusens P, Gevers G.
Genetic determinants of bone mineral content at the spine and radius: a twin study.
Bone.
1987;
8
207-209
-
11
Fang Y, Van Meurs J BJ, Bergink A, Hofman A, Van Dujin C M, Van Leeuwen J PTM, Pols H AP, Utterlinden A G.
Cdx-2 polymorphism in the promoter region of the human vitamin D receptor gene determines susceptibility to fracture in the elderly.
J Bone Miner Res.
2003;
18
1632-1641
-
12
Feskanich D, Willett W, Colditz G.
Walking and leisure-time activity and risk of hip fracture in postmenopausal women.
JAMA.
2002;
288
2300-2306
-
13
Geusens P, Vandevyver C, Vanhoof J, Cassiman J J, Boonen S, Raus J.
Quadriceps and grip strength are related to vitamin D receptor genotype in elderly nonobese women.
J Bone Miner Res.
1997;
12
2082-2088
-
14
Hallal P C, Victora C G, Wells J C, Lima R C.
Physical inactivity: prevalence and associated variables in Brazilian adults.
Med Sci Sports Exerc.
2003;
35
1894-1900
-
15
Johnell O, Kanis J A.
An estimate of the worldwide prevalence, mortality and disability associated with hip fracture.
Osteoporos Int.
2004;
15
897-902
-
16
Kelley G A.
Exercise and regional bone mineral density in postmenopausal women: a meta-analytic review of randomized trials.
Am J Phys Med Rehabil.
1998;
77
76-87
-
17
Li Y C, Amling M, Pirro A E, Priemel M, Meuse J, Baron R, Delling G, Demay M B.
Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice.
Endocrinology.
1998;
139
4391-4396
-
30
Lins T CL, Nogueira L R, Lima R M, Gentil P, Oliveira R J, Pereira R W.
A multiplex single-base extension protocol for genotyping Cdx2, Fokl, Bsml, Apal, and Taql polymorphisms of the vitamin D receptor gene.
Genet Mol Res.
2007;
6
216-224
-
18
Liu Y Z, Liu Y J, Recker R R, Deng H W.
Molecular studies of identification of genes for osteoporosis: the 2002 update.
J Endocrinol.
2003;
177
147-196
-
19
Livshits G, Karasik D, Pavlovsky O, Kobyliansky E.
Segregation analysis reveals a major gene effect in compact and cancellous bone mineral density in 2 populations.
Hum Biol.
1999;
71
155-172
-
20
Marshall D, Johnell O, Wedel H.
Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures.
BMJ.
1996;
312
1254-1259
-
21
Matsudo S, Araújo T, Matsudo V, Andrade D, Andrade E, Oliveira L C, Braggion G.
Questionário Internacional de atividade física (IPAQ): estudo de validade e reprodutibilidade no Brasil.
Rev Bras Ativ Fís Saúde.
2001;
6
5-18
-
22
Miller S A, Dykes D D, Polesky H F.
A simple salting out procedure for extracting DNA from human nucleated cells.
Nucleic Acids Res.
1998;
16
1215
-
23
Morita A, Iki M, Dohi Y, Ikeda Y, Kagamimori S, Kagawa Y, Yoneshima H.
Effects of the Cdx-2 polymorphism of the vitamin D receptor gene and lifestyle factors on bone mineral density in a representative sample of Japanese women: the Japanese Population-based Osteoporosis (JPOS) Study.
Calcif Tissue Int.
2005;
77
339-347
-
24
NIH - National Institute of Health .
Osteoporosis, prevention, diagnosis and therapy.
NIH Consens Statement.
2000;
17
1-45
-
25
Pate R R, Pratt M, Blair S N, Haskell W L, Macera C A, Bouchard C, Buchner D, Ettinger W, Heath G W, King A C, Kriska A, Leon A S, Marcus B H, Morris J, Paffenberger R S, Patrick K, Pollock M L, Rippe J M, Sallis J, Wilmore J H.
Physical activity and public health. A recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine.
JAMA.
1995;
273
402-407
-
26
Puntila E, Kroger H, Lakka T, Tuppurainen M, Jurvelin J, Honkanen R.
Leisure-time physical activity and rate of bone loss among peri- and postmenopausal women: a longitudinal study.
Bone.
2001;
29
442-446
-
27
Ralston S H.
Genetic control of susceptibility to osteoporosis.
J Clin Endocrinol Metab.
2002;
87
2460-2466
-
28
Slemenda C W, Christian J C, Williams C J, Norton J A, Johnston Jr C C.
Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates.
J Bone Miner Res.
1991;
6
561-567
-
29
Sooy K, Sabbagh Y, Demay M B.
Osteoblasts lacking the vitamin D receptor display enhanced osteogenic potential in vitro.
J Cell Biochem.
2005;
94
81-87
-
31
Tsai H J, Choudhry S, Naqvi M, Rodriguez-Cintron W, Burchard E G, Ziv E.
Comparison of three methods to estimate genetic ancestry and control for stratification in genetic association studies among admixed populations.
Hum Genet.
2005;
118
424-433
-
32 USDHHS - U.S. Department Of Health And Human Services .Physical Activity and Health: A Report of the Surgeon General. Atlanta, GA; U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion 1996
-
33
Wolfarth B, Bray M S, Hagberg J M, Perusse L, Rauramaa R, Rivera M A, Roth S M, Rankinen T, Bouchard C.
The human gene map for performance and health-related fitness phenotypes: the 2004 update.
Med Sci Sports Exerc.
2005;
37
881-903
-
34
Yamamoto H, Miamoto K I, Li B, Taketani Y, Kitano M, Inoue Y, Morita K, Pike J W, Takeda E.
The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor gene expression in the small intestine.
J Bone Miner Res.
1999;
14
240-247
Mr.
Paulo Gentil
Programa de Pós Graduação em Educação Física
Universidade Católica de Brasília
QS 07 lote 01 EPCT
71.966 - 700 Taguatinga
Brazil
Phone: + 55 61 33 56 93 56
Fax: + 55 61 33 56 93 56
Email: paulogentil@hotmail.com