We sought evidence of interaction between single nucleotide polymorphisms (SNPs) in the Calcium Sensing Receptor (CASR) gene and early life in determination of bone mineral density (BMD) among individuals from the Hertfordshire Cohort Study.
Four hundred and 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 SNPs 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 analysed.
Among women the 11 genotype of the CASRV3 SNP was associated with higher lumbar spine BMD within the lowest birth-weight tertile, while the opposite pattern was observed among individuals in the highest birth-weight tertile (test for interaction on 1df, p=0.005, adjusted for age, BMI, physical activity, dietary calcium intake, cigarette and alcohol consumption, social class, menopausal status and HRT use). Similar relationships were seen at the total femur (p=0.042, fully adjusted) with birth-weight and at the total femur according to weight at one 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.
We have found evidence of an interaction between a SNP of the CASR gene and birth weight in determination of bone mass in a UK female population.