Tzakas Peter, Wong Betty Y L, Logan Alexander G, Rubin Laurence A, Cole David E C
Dept. of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
BMC Musculoskelet Disord. 2005 Jun 14;6:29. doi: 10.1186/1471-2474-6-29.
Variance of peak bone mass has a substantial genetic component, as has been shown with twin studies examining quantitative measures such as bone mineral density (BMD) and quantitative ultrasound (QUS). Evidence implicating single nucleotide polymorphisms (SNPs) of the transforming growth factor beta-1 (TGFB1) gene is steadily accumulating. However, a comprehensive look at multiple SNPs at this locus for their association with indices of peak bone mass has not been reported.
A cohort of 653 healthy Caucasian females 18 to 35 years old was genotyped for seven TGFB1 SNPs. Polymorphisms were detected by restriction endonuclease digestion of amplified DNA segments.
The frequencies of the least common allele at G-800A, C-509T, codon 10 (L10P), codon 25 (R25P), codon 263 (T263I), C861-20T, and 713-8 delC loci were 0.07, 0.33, 0.41, 0.08, 0.04, 0.25 and 0.01, respectively. A significant association was seen between QUS Stiffness Index (QUS-SI) and the SNP at codon 10 and the linked promoter SNP, C-509T. This association remained significant after multiple regression was used to incorporate important clinical covariates--age, BMI, level of activity, family history, and caffeine intake--into the model.
The association of QUS-SI with -509T is consistent with a gene-dose effect, while only individuals homozygous for the codon 10P allele showed a significant increase. In this cohort of young healthy Caucasian females, the T allele at position -509 is associated with greater bone mass as measured by calcaneal ultrasound.
峰值骨量的差异有很大的遗传成分，对骨矿物质密度（BMD）和定量超声（QUS）等定量指标进行研究的双胞胎研究已证明了这一点。涉及转化生长因子β-1（TGFB1）基因单核苷酸多态性（SNP）的证据在不断积累。然而，尚未有关于该基因座多个SNP与峰值骨量指标相关性的全面研究报道。
对653名年龄在18至35岁的健康白人女性队列进行7个TGFB1 SNP的基因分型。通过对扩增的DNA片段进行限制性内切酶消化来检测多态性。
G-800A、C-509T、密码子10（L10P）、密码子25（R25P）、密码子263（T263I）、C861-20T和713-8 delC基因座上最不常见等位基因的频率分别为0.07、0.33、0.41、0.08、0.04、0.25和0.01。定量超声硬度指数（QUS-SI）与密码子10处的SNP以及与之连锁的启动子SNP C-509T之间存在显著相关性。在将年龄、体重指数、活动水平、家族史和咖啡因摄入量等重要临床协变量纳入模型进行多元回归后，这种相关性仍然显著。
QUS-SI与-509T的相关性符合基因剂量效应，而只有密码子10P等位基因的纯合个体显示出显著增加。在这个年轻健康白人女性队列中，通过跟骨超声测量，-509位点的T等位基因与更高的骨量相关。
