Association between LGR4 polymorphisms and peak bone mineral density and body composition
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ORIGINAL ARTICLE
Association between LGR4 polymorphisms and peak bone mineral density and body composition Wei‑jia Yu1,3 · Zeng Zhang2 · Wen‑zhen Fu1 · Jin‑wei He1 · Chun Wang1 · Zhen‑Lin Zhang1 Received: 7 September 2019 / Accepted: 1 April 2020 © The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2020
Abstract Introduction Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) could affect differentiation of osteoblasts and bone mass through potentiating Wnt/β-catenin signaling. LGR4 is also relevant to glycolipid metabolism. The present study aims to explore the relationship between genetic variations in LGR4 gene and peak bone mineral density (peak BMD) and body composition phenotypes in Chinese nuclear families. Materials and methods 22 single-nucleotide polymorphisms (SNPs) were selected and five blocks were constructed in LGR4. Body composition (lean mass and fat mass) and peak BMD were measured by dual-energy X-ray absorptiometry (DXA). Quantitative transmission disequilibrium test (QTDT) analysis was used to explore the relationship between LGR4 genotypes and the mentioned phenotypes. Results For QTDT analysis after 1000 permutations, significant within-family associations were observed between rs11029986 and total fat mass (TFM) and percentage of TFM (PFM) (P = 0.014 and 0.011, respectively), rs12787344, rs4128868, rs4923445, and rs7936621 and body mass index (BMI) (P = 0.008, 0.003, 0.046, and 0.003, respectively), rs11029986 and total hip BMD (P = 0.026), and rs12796247, rs2219783, and lumbar spine BMD (P = 0.013 and 0.027, respectively). Haplotypes GCGT and AAGC (both in block 3) were observed in significant within-family association with BMI (P = 0.003 and 0.002, respectively). Conclusion It is the first family-based association analysis to explore and demonstrate significant associations between LGR4 genotypes and variations of peak BMD and body composition in young Chinese men. The results are consistent with the findings that recent studies revealed, and confirm the critical relationship between LGR4 gene and both BMD and body composition. Keywords LGR4 · Fat mass · Lean mass · Peak bone mineral density · Quantitative transmission disequilibrium test
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00774-020-01106-0) contains supplementary material, which is available to authorized users. * Chun Wang [email protected] * Zhen‑Lin Zhang [email protected] 1
Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated the Sixth People’s Hospital, 600 Yi‑Shan Rd, Shanghai 200233, People’s Republic of China
Osteoporosis has become a growing public issue throughout the world, causing an enormous social and economic burden [1, 2]. This disorder is associated with impaired bone health and subsequent high risk of fracture. To figure 2
Department of Orthopedic Surgery, Shanghai Jiao Tong Unive
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