title: Genetic factors influencing bone mineral content in a black South African population.
abstract: Bone mass differs according to ethnic classification, with individuals of African ancestry attaining the highest measurements across numerous skeletal sites. Elevated bone mass is even maintained in those individuals exposed to adverse environmental factors, suggesting a prominent genetic effect that may have clinical or therapeutic value. Using a candidate gene approach, we investigated associations of six candidate genes (ESR1, TNFRSF11A, TNFRSF11B, TNFSF11, SOST and SPP1) with bone mass at the hip and lumbar spine amongst pre-pubertal black South African children (mean age 10.6 years) who formed part of the longitudinal Birth to Twenty cohort. 151 black children were genotyped at 366 polymorphic loci, including 112 previously associated and 254 tagging single nucleotide polymorphisms (SNPs). Linear regression was used to highlight significant associations whilst adjusting for height, weight, sex and bone area. Twenty-seven markers (8 previously associated and 19 tag SNPs; P < 0.05) were found to be associated with either femoral neck (18) or lumbar spine (9) bone mineral content. These signals were derived from three genes, namely ESR1 (17), TNFRSF11B (9) and SPP1 (1). One marker (rs2485209) maintained its association with the femoral neck after correction for multiple testing (P = 0.038). When compared to results amongst Caucasian adults, we detected differences with respect to associated skeletal sites. Allele frequencies and linkage disequilibrium patterns were also significantly different between populations. Hence, our results support the existence of a strong genetic effect acting at the femoral neck in black South African children, whilst simultaneously highlighting possible causes that account for inter-ethnic bone mass diversity.
authors.affiliation: Division of Human Genetics, School of Pathology, Faculty of Health Sciences, National Health Laboratory Service, University of the Witwatersrand, Watkins-Pitchford Building, Room 109, Cnr Hospital and De Korte Street, Braamfontein, 2000, Johannesburg, South Africa.
authors.forename: Andrew
authors.initials: A
authors.lastname: May
authors.forename: John M
authors.initials: JM
authors.lastname: Pettifor
authors.forename: Shane A
authors.initials: SA
authors.lastname: Norris
authors.forename: Michèle
authors.initials: M
authors.lastname: Ramsay
authors.forename: Zané
authors.initials: Z
authors.lastname: Lombard
mesh_terms: D044383:Black People / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D002648:Child; D005260:Female; D005272:Femur Neck / Q000502:physiology*; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006615:Hip / Q000502:physiology*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008159:Lumbar Vertebrae / Q000502:physiology*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics