Lips Mirjam A, Syddall Holly E, Gaunt Tom R, Rodriguez Santiago, Day Ian N M, Cooper Cyrus, Dennison Elaine M
MRC Epidemiology Resource Centre, University of Southampton, UK.
J Rheumatol. 2007 Apr;34(4):769-75. Epub 2007 Feb 15.
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.
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.
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.
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.
我们在赫特福德郡队列研究的个体中，探寻钙敏感受体（CASR）基因单核苷酸多态性（SNP）与早期生活在骨密度（BMD）测定中的相互作用证据。
招募了498名男性和468名年龄在59 - 71岁的女性。进行了生活方式问卷调查，并测量了腰椎和股骨颈的骨密度。使用标准提取技术从全血样本中获取DNA。分析了CASR基因的五个SNP，分别称为CASRV1（rs1801725，G→T，S986A）、CASRV2（rs7614486，T→G，非翻译区）(CASRV3)（rs4300957，非翻译区）、(CASRV4)（rs3804592 G→A，内含子）和(CASRV5)（rs1393189，T→C，内含子）。
在女性中，(CASRV3) SNP的11基因型与出生体重最低三分位数组中较高的腰椎骨密度相关，而在出生体重最高三分位数组的个体中观察到相反的模式（1自由度交互作用检验，(p = 0.005)，校正了年龄、体重指数、身体活动、膳食钙摄入量、吸烟和饮酒、社会阶层、绝经状态以及激素替代疗法的使用情况）。在总股骨处观察到与出生体重类似的关系（(p = 0. 042)，完全校正），并且在女性中根据1岁时体重三分位数在总股骨处也观察到类似关系（(p < 0.001)，完全校正）。一种单倍型与女性腰椎骨密度相关（(p = 0.008)，完全校正）；这些发现已在第二个队列中得到重复。
我们发现了在英国女性人群中，CASR基因的一个SNP与出生体重在骨量测定中存在相互作用的证据。
