Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Pediatrics
Published in: BMC Pediatrics 1/2021

Open Access 01-12-2021 | Research Article

Genetic variants and physical activity interact to affect bone density in Hispanic children

Authors: Ruixue Hou, Shelley A. Cole, Mariaelisa Graff, Yujie Wang, Karin Haack, Sandra Laston, Nitesh R. Mehta, Roman J. Shypailo, Margaret L. Gourlay, Anthony G. Comuzzie, Kari E. North, Nancy F. Butte, Venkata Saroja Voruganti

Published in: BMC Pediatrics | Issue 1/2021

Login to get access

Abstract

Background

Our aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study.

Methods

Physical activity and dietary intake were measured by accelerometers and multiple-pass 24 h dietary recalls, respectively. Total body and lumbar spine BMD were measured by dual energy X-ray absorptiometry. A polygenic risk score (PRS) was computed based on SNPs identified in published literature. Regression analysis was conducted with PRSs, MVPA and calcium intake with total body and lumbar spine BMD.

Results

We found evidence of statistically significant interaction effects between the PRS and MVPA on total body BMD and lumbar spine BMD (p < 0.05). Higher PRS was associated with a lower total body BMD (β = − 0.040 ± 0.009, p = 1.1 × 10− 5) and lumbar spine BMD (β = − 0.042 ± 0.013, p = 0.0016) in low MVPA group, as compared to high MVPA group (β = − 0.015 ± 0.006, p = 0.02; β = 0.008 ± 0.01, p = 0.4, respectively).

Discussion

The study indicated that calcium intake does not modify the relationship between genetic variants and BMD, while it implied physical activity interacts with genetic variants to affect BMD in Hispanic children. Due to limited sample size of our study, future research on gene by environment interaction on bone health and functional studies to provide biological insights are needed.

Conclusions

Bone health in Hispanic children with high genetic risk for low BMD is benefitted more by MVPA than children with low genetic risk. Our results may be useful to predict disease risk and tailor dietary and physical activity advice delivery to people, especially children.
Appendix
Available only for authorised users
Literature
1.
Bonjour J-P, Chevalley T, Ferrari S, Rizzoli R. The importance and relevance of peak bone mass in the prevalence of osteoporosis. Salud Publica Mex. 2009;51:s5–17.PubMedCrossRef
2.
Gunter KB, Almstedt HC, Janz KF. Physical activity in childhood may be the key to optimizing lifespan skeletal health. Exerc Sport Sci Rev. 2012;40:13.PubMedPubMedCentralCrossRef
3.
Ilich JZ, Kerstetter JE. Nutrition in bone health revisited: a story beyond calcium. J Am Coll Nutr. 2000;19:715–37.PubMedCrossRef
4.
Duke J, Huhman M, Heitzler C. Physical activity levels among children aged 9-13 years-United States, 2002. JAMA. 2003;290:1308.CrossRef
5.
Jackson KA, Savaiano DA. Lactose Maldigestion, calcium intake and osteoporosis in African-, Asian-, and Hispanic-Americans. J Am Coll Nutr. 2001;20:198S–207S.PubMedCrossRef
6.
Bonjour J-P, Chevalley T, Rizzoli R, Ferrari S. Gene-environment interactions in the skeletal response to nutrition and exercise during growth. Med Sport Sci. 2007;51:64–80.PubMedCrossRef
7.
Ferrari S, Karasik D. Gene--diet interactions on bone. In: Holick MF, Nieves JW, editors. Nutrition and bone health. New York: Springer New York; 2015. p. 21–36.CrossRef
8.
Mitchell JA, Chesi A, Elci O, McCormack SE, Roy SM, Kalkwarf HJ, et al. Physical activity benefits the skeleton of children genetically predisposed to lower bone density in adulthood. J Bone Miner Res. 2016;31:1504–12.PubMedCrossRef
9.
Butte NF, Cai GW, Cole SA, Comuzzie AG. Viva la Familia study: genetic and environmental contributions to childhood obesity and its comorbidities in the Hispanic population. Am J Clin Nutr. 2006;84:646–54.PubMedCrossRef
10.
Voruganti VS, Laston S, Haack K, Mehta NR, Cole SA, Butte NF, et al. Serum uric acid concentrations and SLC2A9 genetic variation in Hispanic children: the viva La Familia study. Am J Clin Nutr April. 2015;101:725–32.CrossRef
11.
Cai G, Cole SAA, Butte N, Bacino C, Diego V, Tan K, et al. A quantitative trait locus on chromosome 18q for physical activity and dietary intake in Hispanic children. Obesity (Silver Spring). 2006;14:1596–604.CrossRef
12.
Butte NF, Cai G, Cole SA, Wilson TA, Fisher JO, Zakeri IF, et al. Metabolic and behavioral predictors of weight gain in Hispanic children: the viva la Familia study. Am J Clin Nutr. 2007;85:1478–85.PubMedCrossRef
13.
Wilson TA, Adolph AL, Butte NF. Nutrient adequacy and diet quality in non-overweight and overweight Hispanic children of low socioeconomic status: the viva la Familia study. J Am Diet Assoc. 2009;109:1012–21.PubMedPubMedCentralCrossRef
14.
Hou R, Cole SA, Graff M, Haack K, Laston S, Comuzzie AG, et al. Genetic variants affecting bone mineral density and bone mineral content at multiple skeletal sites in Hispanic children. Bone. 2020;132:115175.CrossRefPubMed
15.
Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R, et al. CDC growth charts. Adv Data. 2000;2000(314):1–27.
16.
Antiretroviral therapy of HIV infection in infants and children: towards universal access: recommendations for a public health approach-2010 revision. World Health Organization. 2010. pp 1-94. ISBN-978-82-4-15-9980-1.
17.
Medina-Gomez C, Kemp JP, Trajanoska K, Luan J, Chesi A, Ahluwalia TS, et al. Life-course genome-wide association study meta-analysis of Total body BMD and assessment of age-specific effects. Am J Hum Genet. 2018;102:88–102.PubMedPubMedCentralCrossRef
18.
Mitchell JA, Cousminer DL, Zemel BS, Grant SFA, Chesi A. Genetics of pediatric bone strength. Bonekey Rep. 2016;5:1–6.CrossRef
19.
Evans DM, Visscher PM, Wray NR. Harnessing the information contained within genome-wide association studies to improve individual prediction of complex disease risk. Hum Mol Genet. 2009;18:3525–31.PubMedCrossRef
20.
Kemp JP, Medina-Gomez C, Estrada K, St Pourcain B, Heppe DH, Warrington NM, et al. Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment. PLoS Genet. 2014;10(6):e1004423.PubMedPubMedCentralCrossRef
21.
Kocks J, Ward K, Mughal Z, Moncayo R, Adams J, Högler W. Z-score comparability of bone mineral density reference databases for children. J Clin Endocrinol Metab. 2010;95:4652–9.PubMedCrossRef
22.
Leonard MB, Propert KJ, Zemel BS, Stallings VA, Feldman HI. Discrepancies in pediatric bone mineral density reference data: potential for misdiagnosis of osteopenia. J Pediatr. 1999;135(2 Pt 1):182–8.PubMedCrossRef
23.
2018 Physical Activity Guidelines Advisory Committee. 2018 Physical Activity Guidelines Advisory Committee Scientific Report. 2018.
24.
Binkovitz LA, Henwood MJ. Pediatric DXA: Technique and interpretation. Pediatr Radiol. 2007;37:21–31.PubMedCrossRef
25.
Lin DY, Tao R, Kalsbeek WD, Zeng D, Gonzalez F, Fernández-Rhodes L, et al. Genetic association analysis under complex survey sampling: the Hispanic community health study/study of Latinos. Am J Hum Genet. 2014;95:675–88.PubMedPubMedCentralCrossRef
26.
Ross CA, Taylor CL, Yaktine AL, del Vale HB. Committee to review dietary reference intakes for vitamin D and calcium food and nutrition board; Institute of Medicine. Diet Ref Intakes Calcium Vitam D. The National Academies Press; 2010.
27.
Burckhardt P, Dawson-Hughes B, Weaver C. Nutritional influences on bone health; 2010.CrossRef
28.
Piercy KL, Troiano RP, Ballard RM, Carlson SA, Fulton JE, Galuska DA, et al. The physical activity guidelines for Americans. JAMA. 2018;320:2020–8.PubMedCrossRef
29.
Suuriniemi M, Mahonen A, Kovanen V, Alén M, Lyytikäinen A, Wang Q, et al. Association between exercise and pubertal BMD is modulated by estrogen receptor α genotype. J Bone Miner Res. 2004;19:1758–65.PubMedCrossRef
30.
Tajima O, Ashizawa N, Ishii T, Amagai H, Mashimo T, Liu LJ, et al. Interaction of the effects between vitamin D receptor polymorphism and exercise training on bone metabolism. J Appl Physiol. 2000;88:1271–6.PubMedCrossRef
31.
Estrada K, Styrkarsdottir U, Evangelou E, Hsu Y-H, Duncan EL, Ntzani EE, et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012;44:491–501.PubMedPubMedCentralCrossRef
32.
Kukielka M, Holycross B, Billman GE. Endurance exercise training reduces cardiac sodium/calcium exchanger expression in animals susceptible to ventricular fibrillation. Front Physiol. 2011;2:3.PubMedPubMedCentralCrossRef
33.
Willems SM, Wright DJ, Day FR, Trajanoska K, Joshi PK, Morris JA, et al. Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. Nat Commun. 2017;8:16015.PubMedPubMedCentralCrossRef
34.
Cunha TF, Moreira JBN, Paixao NA, Campos JC, Monteiro AWA, Bacurau AVN, et al. Aerobic exercise training upregulates skeletal muscle calpain and ubiquitin-proteasome systems in healthy mice. J Appl Physiol. 2012;112:1839–46.PubMedCrossRef
35.
Taillandier D, Combaret L, Pouch M-N, Samuels SE, Béchet D, Attaix D. The role of ubiquitin–proteasome-dependent proteolysis in the remodelling of skeletal muscle. Proc Nutr Soc. 2004;63:357–61.PubMedCrossRef
36.
Schönau E, Werhahn E, Schiedermaier U, Mokow E, Schiessl H, Scheidhauer K, et al. Influence of muscle strength on bone strength during childhood and adolescence. Horm Res Paediatr. 1996;45(Suppl. 1):63–6.
37.
Sabik OL, Farber CR. Using GWAS to identify novel therapeutic targets for osteoporosis. Transl Res. 2017;181:15–26.PubMedCrossRef
38.
Chevalley T, Bonjour JP, Ferrari S, Hans D, Rizzoli R. Skeletal site selectivity in the effects of calcium supplementation on areal bone mineral density gain: a randomized, double-blind, placebo-controlled trial in prepubertal boys. J Clin Endocrinol Metab. 2005;90:3342–9.PubMedCrossRef
39.
Bonjour J-P, Carrie A-L, Ferrari S, Clavien H, Slosman D, Theintz G, et al. Calcium-enriched foods and bone mass growth in prepubertal girls: a randomized, double-blind, placebo-controlled trial. J Clin Invest. 1997;99:1287–94.PubMedPubMedCentralCrossRef
40.
Thouverey C, Caverzasio J. Focus on the p38 MAPK signaling pathway in bone development and maintenance. Bonekey Rep. 2015;4:1–8.CrossRef
41.
Livingstone MBE, Robson PJ. Measurement of dietary intake in children. Proc Nutr Soc. 2000;59:279–93.PubMedCrossRef
42.
Palaniappan U, Cue RI, Payette H, Gray-Donald K. Implications of day-to-day variability on measurements of usual food and nutrient intakes. J Nutr. 2003;133:232–5.PubMedCrossRef
43.
Migueles JH, Cadenas-Sanchez C, Ekelund U, Nyström CD, Mora-Gonzalez J, Löf M, et al. Accelerometer data collection and processing criteria to assess physical activity and other outcomes: a systematic review and practical considerations. Sport Med. 2017;47:1821–45.CrossRef
44.
Harvey NC, Cole ZA, Crozier SR, Kim M, Ntani G, Goodfellow L, et al. Physical activity, calcium intake and childhood bone mineral: a population-based cross-sectional study. Osteoporos Int. 2012;23:121–30.PubMedCrossRef
45.
46.
Trost SG. State of the art reviews: measurement of physical activity in children and adolescents. Am J Lifestyle Med. 2007;1:299–314.CrossRef
Metadata
Title
Genetic variants and physical activity interact to affect bone density in Hispanic children
Authors
Ruixue Hou
Shelley A. Cole
Mariaelisa Graff
Yujie Wang
Karin Haack
Sandra Laston
Nitesh R. Mehta
Roman J. Shypailo
Margaret L. Gourlay
Anthony G. Comuzzie
Kari E. North
Nancy F. Butte
Venkata Saroja Voruganti
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2021
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-021-02537-y

Other articles of this Issue 1/2021

BMC Pediatrics 1/2021 Go to the issue

Research

Traditional Mongolian swaddling and developmental dysplasia of the hip: a randomized controlled trial

Research

A multicenter study of incidence, risk factors and outcomes of babies with birth asphyxia in Nepal

Research article

Pediatric dentists’ perspectives of children with special health care needs in Japan: developmental disabilities, phobia, maltreatment, and multidisciplinary collaboration

Research article

Effect of improved cookstove intervention on childhood acute lower respiratory infection in Northwest Ethiopia: a cluster-randomized controlled trial

Study protocol

Advance care planning for adolescents with cancer and their parents: study protocol of the BOOST pACP multi-centre randomised controlled trial and process evaluation

Research

The effects of exposure to HIV in neonates at a referral hospital in South Africa