Interaction between birthweight and polymorphism in the calcium-sensing receptor gene in determination of adult bone mass: the Hertfordshire cohort study


Lips, Mirjam A., Syddall, Holly E., Gaunt, Tom R., Rodriguez, Santiago, Day, Ian N.M., Cooper, Cyrus, Dennison, Elaine M. and Southampton Genetic Epidemology Research Group, (2007) Interaction between birthweight and polymorphism in the calcium-sensing receptor gene in determination of adult bone mass: the Hertfordshire cohort study. Journal of Rheumatology, 34, (4), 769-775.

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Description/Abstract

OBJECTIVE: We sought evidence of interaction between single-nucleotide polymorphisms (SNP) in the calcium-sensing receptor (CASR) gene and early life in determination of bone mineral density (BMD) among individuals from the Hertfordshire Cohort Study. METHODS: Four hundred ninety-eight men and 468 women aged 59-71 years were recruited. A lifestyle questionnaire was administered and BMD at lumbar spine and femoral neck was measured. DNA was obtained from whole blood samples using standard extraction techniques. Five SNP of the CASR gene termed CASRV1 (rs1801725, G-->T, S986A), CASRV2 (rs7614486, T-->G, untranslated), CASRV3 (rs4300957, untranslated), CASRV4 (rs3804592 G-->A, intron), and CASRV5 (rs1393189, T-->C, intron) were analyzed. RESULTS: Among women the 11 genotype of the CASRV3 SNP was associated with higher lumbar spine BMD within the lowest birthweight tertile, while the opposite pattern was observed among individuals in the highest birthweight tertile (test for interaction on 1 df, p = 0.005, adjusted for age, body mass index, physical activity, dietary calcium intake, cigarette and alcohol consumption, social class, menopausal status, and hormone replacement therapy use). Similar relationships were seen at the total femur (p = 0.042, fully adjusted) with birthweight and at the total femur according to weight at 1 year tertile among women (p < 0.001, fully adjusted). One haplotype was associated with lumbar spine BMD in women (p = 0.008, fully adjusted); these findings were replicated in a second cohort. CONCLUSION: We have found evidence of an interaction between a SNP of the CASR gene and birthweight in determination of bone mass in a UK female population.

Item Type: Article
ISSNs: 1499-2752 (print)
Related URLs:
Keywords: femur, early-life, weight, cohort studies, bone mass, social class, bone, methods, activity, cohort, aged, women, calcium, blood, gene, neck, body mass index, female, adult, dna, genotype, alcohol, therapy, hertfordshire
Subjects: R Medicine > RZ Other systems of medicine
Q Science > QH Natural history > QH426 Genetics
R Medicine > RA Public aspects of medicine
Divisions: University Structure - Pre August 2011 > School of Medicine > Developmental Origins of Health and Disease
University Structure - Pre August 2011 > School of Medicine > Human Genetics
ePrint ID: 61335
Date Deposited: 01 Oct 2008
Last Modified: 27 Mar 2014 18:43
URI: http://eprints.soton.ac.uk/id/eprint/61335

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