title: 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 alpha (ERalpha), 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 ERa (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.
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China. dengfeiyan@hotmail.com
authors.forename: Fei-Yan
authors.initials: FY
authors.lastname: Deng
authors.forename: Ji-Rong
authors.initials: JR
authors.lastname: Long
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Lei
authors.forename: Miao-Xin
authors.initials: MX
authors.lastname: Li
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001798:Blood Proteins / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D002681:China; D003094:Collagen / Q000235:genetics; D024042:Collagen Type I; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D010281:Parathyroid Hormone / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018167:Receptors, Calcitriol / Q000235:genetics; D055815:Young Adult; D060749:alpha-2-HS-Glycoprotein
chemical_list: C556354:AHSG protein, human; D001798:Blood Proteins; D024042:Collagen Type I; D047628:Estrogen Receptor alpha; D015850:Interleukin-6; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D060749:alpha-2-HS-Glycoprotein; D015675:Osteocalcin; D003094:Collagen