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01-01-2006 | Original Article

Genetic determination and correlation of body mass index and bone mineral density at the spine and hip in Chinese Han ethnicity

Authors: Fei-Yan Deng, Shu-Feng Lei, Miao-Xin Li, Cheng Jiang, Volodymyr Dvornyk, Hong-Wen Deng

Published in: Osteoporosis International | Issue 1/2006

Abstract

The purpose of the present study was to evaluate the magnitude of genetic determination of spine and hip bone mineral density (BMD) and body mass index (BMI), and to explore the genetic, environmental, and phenotypic correlations among the above phenotypes in Chinese Han ethnicity. The sample was composed of at least 217 complete nuclear families in Chinese Han ethnicity. BMD at the spine and hip was measured using a dual-energy X-ray absorptiometry scanner. The heritability ( h ²) of BMI and BMD at the spine and hip, the genetic correlation ( ρ _G) and environmental correlation ( ρ _E) among the three phenotypes were evaluated via variance analysis, with age, sex, and age-by-sex interaction as covariates. The phenotypic correlation ( ρ _P) and the bivariate heritability ρ_G ² were also calculated. The heritability for BMD and BMI was ~0.70 and ~0.50, respectively ( p <0.0001). The common environment shared by household members (household effect) is significant for BMI variation ( p =0.0004). Significant genetic, environmental, and phenotypic correlation was observed. The ρ_G ² values were 0.13 for BMI/spine BMD, 0.18 for BMI/hip BMD, and 0.58 for the spine BMD/hip BMD. While BMD at the spine and hip have significant genetic determination, BMI is more likely to be affected by environmental factors than BMD. In addition, BMD at the spine and hip shares more genetic effect (pleiotropy) than BMI and BMD do in Chinese Han ethnicity, though the effects are significant for both.

Liu Z, Piao J, Pang L, Qing X, Nan S, Pan Z, Guo Y, Wang X, Li F, Liu J, Cheng X (2002) The diagnostic criteria for primary osteoporosis and the incidence of osteoporosis in China. J Bone Miner Metab 20:181–189CrossRefPubMed

People’s Daily Online (2004) China to promote “cocktail weight loss therapy” in response to WHO plan. http://english.peopledaily.com.cn/200205/07/eng20020507_95217.shtml (Beijing) [Last updated: February 28, 2004]

Gueguen R, Jouanny P, Guillemin F, Kuntz C, Pourel J, Siest G (1995) Segregation analysis and variance components analysis of bone mineral density in healthy families. J Bone Miner Res 10:2017–2022ADSPubMedCrossRef

Deng HW, Chen WM, Conway T, Zhou Y, Davies KM, Stegman MR, Deng H, Recker RR (2000) Determination of bone mineral density of the hip and spine in human pedigrees by genetic and life-style factors. Genet Epidemiol 19:160–177CrossRefPubMed

Maes HH, Neale MC, Eaves LJ (1997) Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 27:325–325CrossRefPubMed

Deng HW, Lai DB, Conway T, Li J, Xu FH, Davies KM, Recker RR (2001) Characterization of genetic and lifestyle factors for determining variation in body mass index, fat mass, percentage of fat mass, and lean mass. J Clin Densitom 4:353–361CrossRefMATHPubMed

De Marchi G, Ferraccioli G (2002) Leptin: regulatory role in bone metabolism and in inflammation. Reumatismo 54:217–225

Ricci TA, Heymsfield SB, Pierson RN Jr, Stahl T, Chowdhury HA, Shapses SA (2001) Moderate energy restriction increases bone resorption in obese postmenopausal women. Am J Clin Nutr 73:347–352PubMed

Slemenda CW (1995) Body composition and skeletal density: Mechanical loading or something more? J Clin Endocrinol Metab 80:1761–1763CrossRefPubMed

10.

Vanberesteijn EC, Vanlaarhoven JPRM, Smals AGH (1992) Body weight and/or endogenous estradiol as determinants of cortical bone mass and bone loss in healthy postmenopausal women. Acta Endocrinol 127:226–230

11.

Gimble JM, Nuttall ME (2004) Bone and fat: old questions, new insights. Endocrine 23:183–188CrossRefPubMed

12.

Pei L, Tontonoz P 2004 Fat’s loss is bone’s gain. J Clin Invest 113:805–806

13.

Akune T, Ohba S, Kamekura S, Yamaguchi M, Chung UI, Kubota N, Terauchi Y, Harada Y, Azuma Y, Nakamura K, Kadowaki T, Kawaguchi H (2004) PPAR gamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest 113:846–855CrossRefPubMed

14.

Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML (2001) Osteoporosis-Pseudoglioma Syndrome Collaborative Group. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513–523CrossRefPubMed

15.

Deng FY, Liu MY, Li MX, Lei SF, Qin YJ, Zhou Q, Liu YJ, Deng HW (2003) Tests of linkage and association of the COL1A2 gene with bone phenotypes’ variation in Chinese nuclear families. Bone 33:614–619CrossRefPubMed

16.

Almasy L, Blangero J (1998) Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 62:1198–1211CrossRefPubMed

17.

Lange K, Boehnke M (1983) Extensions to pedigree analysis, IV: covariance component models for multivariate traits. Am J Med Genet 14:513–524CrossRefPubMed

18.

Williams JT, Van Eerdewegh P, Almasy L, Blangero J (1999) Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. I. Likelihood formulation and simulation results. Am J Hum Genet 65:1134–1147CrossRefPubMed

19.

Yao WJ, Wu CH, Wang ST, Chang CJ, Chiu NT, Yu CY (2001) Differential changes in regional bone mineral density in healthy Chinese: age-related and sex-dependent. Calcif Tissue Int 68:330–336CrossRefPubMed

20.

Duncan EL, Cardon LR, Sinsheimer JS, Wass JA, Brown MA (2003) Site and gender specificity of inheritance of bone mineral density. J Bone Miner Res 18:1531–1538CrossRefPubMed

21.

Deng HW, Stegman MR, Davies KM, Conway T, Recker RR (1999) Genetic determination of variation and covariation of peak BMD at hip and spine. J Clin Densitom 2:251–263CrossRefPubMed

22.

Nguyen TV, Howard GM, Kelly PJ, Eisman JA (1998) BMD, lean mass, and fat mass: same genes or same environments? Am J Epidemiol 147:3-16PubMed

23.

Livshits G, Deng HW, Nguyen TV, Yakovenko K, Recker RR, Eisman JA (2004) Genetics of bone mineral density: evidence for a major pleiotropic effect from an intercontinental study. J Bone Miner Res 19:914–923CrossRefPubMed

24.

Howard GM, Nguyen TV, Harris M, Kelly PJ, Eisman JA (1998) Genetic and environmental contributions to the association between quantitative ultrasound and bone mineral density measurements: a twin study. J Bone Miner Res 13:1318–1327CrossRefPubMedMathSciNet

25.

Ducy P, Schinke T, Karsenty G (2000) The osteoblast: a sophisticated fibroblast under central surveillance. Science 289:1501–1504CrossRefADSPubMed

26.

Liu YJ, Araujo S, Recker RR, Deng HW (2003) Molecular and genetic mechanisms of obesity: implications for future management. Curr Mol Med 3:325–340CrossRefPubMed

27.

Reseland JE, Syversen U, Bakke I, Qvigstad G, Eide LG, Hjertner O, Gordeladze JO, Drevon CA (2001) Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization. J Bone Miner Res 16:1426–1433CrossRefPubMed

28.

Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305–317CrossRefPubMed

29.

Holloway WR, Collier FM, Aitken CJ, Myers DE, Hodge JM, Malakellis M, Gough TJ, Collier GR, Nicholson GC (2002) Leptin inhibits osteoclast generation. J Bone Miner Res 17:200–209CrossRefPubMed

30.

Livshits G, Pantsulaia IA, Trofimov S, Kobyliansky E (2003) Genetic variation of circulating leptin is involved in genetic variation of hand bone size and geometry. Osteoporos Int 14:476-483CrossRefPubMed

31.

Thomas T, Burguera B (2002) Is leptin the link between fat and bone mass? J Bone Miner Res 17:1563–1569CrossRefADSPubMed

32.

Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP, Aspden RM, Ralston SH (2001) A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 107:899–907PubMedCrossRef

33.

Huang QY, Shen H, Deng HY, Conway T, Davies KM, Li JL, Recker RR, Deng HW (2003) Linkage and association of the CA repeat polymorphism of the IL6 gene, obesity-related phenotypes, and bone mineral density (BMD) in two independent Caucasian populations. J Hum Genet 48:430–437CrossRefPubMed

34.

Stephens JW, Hurel SJ, Cooper JA, Acharya J, Miller GJ, Humphries SE (2004) A common functional variant in the interleukin-6 gene is associated with increased body mass index in subjects with type 2 diabetes mellitus. Mol Genet Metab 82:180–186CrossRefPubMed

35.

Chiba T, Nakazawa T, Yui K, Kaneko E, Shimokado K (2003) VLDL induces adipocyte differentiation in ApoE-dependent manner. Arterioscler Thromb Vasc Biol 23:1423–1429CrossRefPubMed

36.

Zajickova K, Zofkova I, Hill M, Horinek A, Novakova A (2003) Apolipoprotein E 4 allele is associated with low bone density in postmenopausal women. J Endocrinol Invest 26:312–315PubMed

37.

Kyoko I, Satoshi H, Tsuyoshi I, Takami M, Hirotoshi M, Yoshiki N (2003) Risk factors for osteoporosis in men. J Bone Miner Metab 21:86–90CrossRef

38.

Zhao J, Zhou X, Meng X, Liu G, Xing X, Liu H, Xu L (1997) Polymorphisms of vitamin D receptor gene and its association with bone mineral density and osteocalcin in Chinese. Chin Med J (Engl) 110:366–371

39.

Tofteng CL, Jensen JE, Abrahamsen B, Odum L, Brot C (2002) Two polymorphisms in the vitamin D receptor gene—association with bone mass and 5-year change in bone mass with or without hormone-replacement therapy in postmenopausal women: the Danish Osteoporosis Prevention Study. J Bone Miner Res 17:1535–1544CrossRefPubMed

Title: Genetic determination and correlation of body mass index and bone mineral density at the spine and hip in Chinese Han ethnicity
Authors: Fei-Yan Deng
Shu-Feng Lei
Miao-Xin Li
Cheng Jiang
Volodymyr Dvornyk
Hong-Wen Deng
Publication date: 01-01-2006
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 1/2006
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-005-1930-4

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Genetic determination and correlation of body mass index and bone mineral density at the spine and hip in Chinese Han ethnicity

Abstract

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