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Title: Causal relationship between the AHSG gene and BMD through fetuin-A and BMI: Multiple mediation analysis
Authors: C. Sritara
A. Thakkinstian
B. Ongphiphadhanakul
L. Chailurkit
S. Chanprasertyothin
W. Ratanachaiwong
P. Vathesatogkit
P. Sritara
Mahidol University
Medical and Health Office
Keywords: Medicine
Issue Date: 1-Jan-2014
Citation: Osteoporosis International. Vol.25, No.5 (2014), 1555-1562
Abstract: Summary: Using mediation analysis, a causal relationship between the AHSG gene and bone mineral density (BMD) through fetuin-A and body mass index (BMI) mediators was suggested. Introduction: Fetuin-A, a multifunctional protein of hepatic origin, is associated with bone mineral density. It is unclear if this association is causal. This study aimed at clarification of this issue. Methods: A cross-sectional study was conducted among 1,741 healthy workers from the Electricity Generating Authority of Thailand (EGAT) cohort. The alpha-2-Heremans-Schmid glycoprotein (AHSG) rs2248690 gene was genotyped. Three mediation models were constructed using seemingly unrelated regression analysis. First, the ln[fetuin-A] group was regressed on the AHSG gene. Second, the BMI group was regressed on the AHSG gene and the ln[fetuin-A] group. Finally, the BMD model was constructed by fitting BMD on two mediators (ln[fetuin-A] and BMI) and the independent AHSG variable. All three analyses were adjusted for confounders. Results: The prevalence of the minor T allele for the AHSG locus was 15.2 %. The AHSG locus was highly related to serum fetuin-A levels (P∈<∈0.001). Multiple mediation analyses showed that AHSG was significantly associated with BMD through the ln[fetuin-A] and BMI pathway, with beta coefficients of 0.0060 (95 % CI 0.0038, 0.0083) and 0.0030 (95 % CI 0.0020, 0.0045) at the total hip and lumbar spine, respectively. About 27.3 and 26.0 % of total genetic effects on hip and spine BMD, respectively, were explained by the mediation effects of fetuin-A and BMI. Conclusions: Our study suggested evidence of a causal relationship between the AHSG gene and BMD through fetuin-A and BMI mediators. © 2014 International Osteoporosis Foundation and National Osteoporosis Foundation.
ISSN: 14332965
Appears in Collections:Scopus 2011-2015

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