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ISSN 1672-9145 Acta Biochim Biophys Sin 2005, 37(1): 61–67 CN 31-1940/Q

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Association between VDR ApaI Polymorphism and Hip Bone Mineral Density Can Be Modified by Body Mass Index: A Study on Postmenopausal Chinese Women

Hong XU^1,2, Dong-Hai XIONG³, Fu-Hua XU³, Yuan-Yuan ZHANG³, Shu-Feng LEI¹, and Hong-Wen DENG^1,3*

¹Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China;

²Department of Physiology, Jiangxi Medical College, Nanchang 330006, China;

³Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University Medical Center, Omaha, NE 68131, USA

Abstract Osteoporosis is a major public health problem for old people. Genetic factors are considered to be major contributors to the pathogenesis of postmenopausal osteoporosis. The vitamin D receptor (VDR) gene is a prominent candidate gene for the regulation of postmenopausal bone mass; however, despite extensive studies, controversy remains regarding its association with postmenopausal body mineral density (BMD) variation. In this study, a total of 260 healthy postmenopausal Chinese women were genotyped at the VDR ApaI locus using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Raw hip BMD was significantly associated with VDR ApaI polymorphism with and without adjusting for age (P=0.015 and 0.040, respectively). This genetic effect can explain 3.32% of hip BMD variation. However, the significant association vanished after correcting for both age and body mass index (BMI) (P=0.169). In addition, we observed a significant association between VDR ApaI polymorphism with unadjusted BMI (P=0.042) or BMI adjusted for age (P=0.049). The raw hip BMD was also found to be significantly correlated with BMI (r=0.517, P=0.0001), with BMI explaining 26.35% of the variation of hip BMD. All of these facts prompt us to conclude that the significant association between the VDR ApaI genotype and hip BMD may be modified by BMI in postmenopausal Chinese women. Our findings may partially explain the earlier inconsistent association results concerning the VDR gene and BMD, and highlight the importance of incorporating covariates such as BMI into osteoporosis association studies.

Key words body mass index (BMI); bone mineral density (BMD); genetic association; osteoporosis; vitamin D receptor (VDR) gene

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Received: October 18, 2004 Accepted: December 14, 2004

*Corresponding author: Tel, 86-731-8872791; Fax, 86-731-8872791; E-mail, [email protected]