Association between LGR4 polymorphisms and peak bone mineral density and body composition

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.

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.

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).

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.