Potential effect of inter-genic action on peak bone mass (PBM) in Chinese females

Abstract

Peak bone mass (PBM) is a complex trait, determined by both genetic and environmental factors and also their interactions. Vitamin D receptor (VDR), estrogen receptor α (ERα), interleukin 6 (IL6), parathyroid hormone (PTH), collagen type I alpha 2 (COL1A2), bone Gla protein (BGP), alpha2-HS glycoprotein (AHSG) are among the important candidate genes of bone metabolism. The study aims to detect significant effect of potential inter-genic action underlying PBM in Chinese females. 361 unrelated healthy premenopausal Chinese females (aged 20-44 years) with Han ethnicity were recruited from the Shanghai city in China. Bone mineral density (BMD) at the hip and the lumbar spine (L1-4) was measured using a Hologic QDR 2000 + dual-energy X-ray absorptiometry (DXA) scanner. Eight polymorphisms among the seven genes were genotyped, i. e. Apa I in VDR, Pvu II and Xba I in ERα (ERX and ERP, respectively), BsrB I in IL6, BstB I in PTH, Msp I in COL1A2, Hind III in BGP, and Sac I in AHSG, using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) methods. Two-way analysis of variance (ANOVA) showed significant effects of IL6 x ERP interaction on PBM at the total hip (P = 0.019), intertrochanter (P = 0.016), and femoral neck (P = 0.019). The BMD difference between GGPp carriers and GGpp subjects (at these two loci) amounted to 18.0%, 19.5%, and 14.8% at the hip, intertrochanter,and femoral neck, respectively. The potential interaction effect of AHSG x IL6 was observed on femoral neck PBM (P = 0.046). GGSS individuals (at these two loci) had, on average, 18.8% higher femoral neck BMD than those subjects with GGSs genotype. The population-level statistical analysis indicates that IL6 x ERP and AHSG x IL6 have significant inter-genic effect on the genetic determination of PBM in Chinese females.