Mullin B H, Prince R L, Dick I M, Islam F M A, Hart D J, Spector T D, Devine A, Dudbridge F, Wilson S G
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, 6009.
Osteoporos Int. 2008 Jul;19(7):961-8. doi: 10.1007/s00198-007-0517-7. Epub 2007 Nov 24.
The 1p36 region of the human genome has been identified as containing a QTL for BMD in multiple studies. We analysed the TNFRSF1B gene from this region, which encodes the TNF receptor 2, in two large population-based cohorts. Our results suggest that variation in TNFRSF1B is associated with BMD.
The TNFRSF1B gene, encoding the TNF receptor 2, is a strong positional and functional candidate gene for impaired bone structure through the role that TNF has in bone cells. The aims of this study were to evaluate the role of variations in the TNFRSF1B gene on bone structure and osteoporotic fracture risk in postmenopausal women.
Six SNPs in TNFRSF1B were analysed in a cohort of 1,190 postmenopausal Australian women, three of which were also genotyped in an independent cohort of 811 UK postmenopausal women. Differences in phenotypic means for genotype groups were examined using one-way ANOVA and ANCOVA.
Significant associations were seen for IVS1+5580A>G with BMD and QUS parameters in the Australian population (P = 0.008 - 0.034) and with hip BMD parameters in the UK population (P = 0.005 - 0.029). Significant associations were also observed between IVS1+6528G>A and hip BMD parameters in the UK cohort (P = 0.0002 - 0.003). We then combined the data from the two cohorts and observed significant associations between both IVS1+5580A>G and IVS1+6528G>A and hip BMD parameters (P = 0.002 - 0.033).
Genetic variation in TNFRSF1B plays a role in the determination of bone structure in Caucasian postmenopausal women, possibly through effects on osteoblast and osteoclast differentiation.
在多项研究中，人类基因组的1p36区域已被确定包含一个与骨密度相关的数量性状位点（QTL）。我们在两个基于人群的大型队列中分析了该区域的TNFRSF1B基因，该基因编码肿瘤坏死因子受体2。我们的结果表明，TNFRSF1B基因的变异与骨密度相关。
编码肿瘤坏死因子受体2的TNFRSF1B基因，由于肿瘤坏死因子在骨细胞中的作用，是骨结构受损的一个强有力的位置和功能候选基因。本研究的目的是评估TNFRSF1B基因变异对绝经后妇女骨结构和骨质疏松性骨折风险的作用。
在1190名澳大利亚绝经后妇女队列中分析了TNFRSF1B基因中的6个单核苷酸多态性（SNP），其中3个SNP也在811名英国绝经后妇女的独立队列中进行了基因分型。使用单因素方差分析（ANOVA）和协方差分析（ANCOVA）检查基因型组表型均值的差异。
在澳大利亚人群中，IVS1 + 5580A>G与骨密度和定量超声（QUS）参数之间存在显著关联（P = 0.008 - 0.034），在英国人群中与髋部骨密度参数存在显著关联（P = 0.005 - 0.029）。在英国队列中，IVS1 + 6528G>A与髋部骨密度参数之间也观察到显著关联（P = 0.0002 - 0.003）。然后我们合并了两个队列的数据，观察到IVS1 + 5580A>G和IVS1 + 6528G>A与髋部骨密度参数之间均存在显著关联（P = 0.002 - 0.033）。
TNFRSF1B基因的遗传变异在白种人绝经后妇女骨结构的决定中起作用，可能是通过对成骨细胞和破骨细胞分化的影响。
