title: A new haplotype in BMP4 implicated in ossification of the posterior longitudinal ligament (OPLL) in a Chinese population.
abstract: Previous genome-wide microarray analysis of candidate genes involved in the ossification of the posterior longitudinal ligament (OPLL) of the spine resulted in the identification of a novel, clinically relevant gene encoding bone morphogenetic protein 4 (BMP4) but was defined only by its expression patterns. The complete genomic BMP4 coding DNA from 450 patients with OPLL and 550 matched controls were sequenced and compared. We identified 18 SNPs, among which the minor alleles of SNP8 (C>T; p < 0.001; OR: 1.58), SNP13 (rs17563C>T; p < 0.001; OR: 1.76), and SNP14 (rs76335800A>T; p < 0.001; OR: 1.68) were associated with OPLL. Logistic regression analysis showed that the additive model of SNP8 (p < 0.001; OR: 3.48), SNP13 (p < 0.001; OR: 2.22), and SNP14 (p < 0.001; OR: 1.99) retained statistical significance. Linkage disequilibrium (LD) analysis identified a 3-kbp block of intense LD in BMP4 and 1 specific haplotype, TGGGCTT (p < 0.001, OR: 2.54), which was associated with OPLL-associated risk alleles and increased severity of OPLL, as shown by the distribution of ossified vertebrae in patients with OPLL (p = 0.002). Novel mutations in the BMP4 gene and a specific haplotype TGGGCTT appear to contribute to the risk of developing OPLL. Also the severity of OPLL seems to be mediated predominantly by genetic variations in this specific BMP4 gene region, but might be associated with other certain clinical and demographic characteristics in the Chinese population studied.
authors: Department of Orthopaedics, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
authors: Yuan
authors: Y
authors: Ren
authors: Jie
authors: J
authors: Feng
authors: Zhi-zhong
authors: ZZ
authors: Liu
authors: Hong
authors: H
authors: Wan
authors: Jun-hua
authors: JH
authors: Li
authors: Xin
authors: X
authors: Lin
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D017887:Ossification of Posterior Longitudinal Ligament / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4