Association of a BMP9 haplotype with ossification of the posterior longitudinal ligament (OPLL) in a Chinese population.
Association of a BMP9 haplotype with ossification of the posterior longitudinal ligament (OPLL) in a Chinese population.
复制标题
DOI：
10.1371/journal.pone.0040587
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Ren Y;Liu ZZ;Feng J;Wan H;Li JH;Wang H;Lin X
直接或体外BMP9腺病毒基因治疗可在注射部位诱导大量骨形成，并明显促进脊柱融合。成骨活性的综合分析表明，BMP9是14种人BMPs中体外和体内诱导成骨分化的最有效的诱导剂之一。然而，遗传变异及其是否与OPLL相关并未被考虑。我们测定了450例OPLL患者和550例匹配对照的完整BMP9基因序列。对单标记和单倍型进行分析。其中rs7923671(T&gT；C；P = 0.0026；OR：1.33，CI：1.10~1.6)、rs75024165(C&>T，Thr304 Met；P<；0.001；OR：1.76，CI：1.47~2.12)和rs34379100(A&gT；C；P<；0.001；OR：1.52，CI：1.27~1.82)与OPLL相关。Logistic回归分析显示，rs75024165(TT、CT、CC；P<；0.001；OR：1.74)和rs34379100(CC、AC、AA；P = 0.003；OR：1.95)的相加模型在调整临床和人口学特征后仍具有统计学意义。连锁不平衡(LD)分析发现，BMP9有一个3kb的高强度LD区块和一个特殊的单倍型CTCA(P<；0.001；OR：2.37)，该单倍型含有OPLL相关的风险等位基因，是OPLL的危险因素。OPLL患者椎体骨化的分布表明，这种单倍型与OPLL严重程度的增加有关(P = 0.001)。综上所述，在被研究的中国人群中，BMP9基因中的SNP似乎与某些临床和人口学特征有关，导致OPLL的风险。OPLL的严重程度似乎主要是由具有特定单倍型CTCA的3kb BMP9基因座的遗传变异所介导的。
Direct or ex vivo BMP9 adenoviral gene therapy can induce massive bone formation at the injection sites and clearly promote spinal fusion. A comprehensive analysis of the osteogenic activity indicated that BMP9 was one of the most potent inducers of osteogenic differentiation both in vitro and in vivo among 14 types of human BMPs. However, genetic variations and whether they correlated with OPLL were not considered. We have sequenced the complete BMP9 gene in 450 patients with OPLL and in 550 matched controls. Analyses were performed on single markers and haplotypes. Single marker tests identified 6 SNPs, among which the minor alleles of rs7923671 (T>C; P = 0.0026; OR: 1.33, CI: 1.10–1.60), rs75024165 (C>T, Thr304Met; P<0.001; OR: 1.76, CI: 1.47–2.12) and rs34379100 (A>C; P<0.001; OR: 1.52, CI: 1.27–1.82) were associated with OPLL. Logistic regression analysis showed that the additive model of rs75024165 (TT vs. CT vs. CC; P<0.001; OR: 1.74) and rs34379100 (CC vs. AC vs. AA; P = 0.003; OR: 1.95) retained statistical significance when adjusted for clinical and demographic characteristics. Linkage disequilibrium (LD) analysis identified one 3 kb block of intense LD in BMP9 and one specific haplotype, CTCA (P<0.001; OR: 2.37), that contained the OPLL-associated risk alleles and was a risk factor for OPLL. This haplotype is associated with increased severity of OPLL, as shown by the distribution of ossified vertebrae in patients with OPLL (P = 0.001). In summary, in the Chinese population studied, SNPs in the BMP9 gene appear to contribute to the risk of OPLL in association with certain clinical and demographic characteristics. The severity of OPLL seems to be mediated predominantly by genetic variations in a 3kb BMP9 locus with the specific haplotype CTCA.
登录
查看更多内容
影响因子：
6.2
作者：
Leblanc, Elisabeth;Trensz, Frederic;Grenier, Guillaume
通讯作者：
Grenier, Guillaume
影响因子：
0.9
作者：
Abdelaal, MM;Tholpady, SS;Ogle, RC
通讯作者：
Ogle, RC
影响因子：
2.8
作者：
Luu, Hue H.;Song, Wen-Xin;He, Tong-Chuan
通讯作者：
He, Tong-Chuan
影响因子：
3
作者：
Kawaguchi, Y;Furushima, K;Kimura, T
通讯作者：
Kimura, T
影响因子：
3
作者：
Kobashi, G;Washio, M;Tanaka, H
通讯作者：
Tanaka, H