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首页> 外文期刊>Circulation journal >Common Genetic Variants on Bone Morphogenetic Protein Receptor Type IB (BMPR1B) Gene Are Predictive for Carotid Intima-Media Thickness
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Common Genetic Variants on Bone Morphogenetic Protein Receptor Type IB (BMPR1B) Gene Are Predictive for Carotid Intima-Media Thickness

机译：IB骨形态发生蛋白受体（BMPR1B）基因的常见遗传变异是颈动脉内膜中层厚度的预测。

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Background: Bone morphogenetic proteins (BMP) 2 and 4 are implicated in the development of atherosclerosis. However, the relationships between the proteins, their main receptors and carotid intima-media thickness (cIMT), a predictive preclinical phenotype of atherosclerosis, have not been established. Methods?and?Results: We screened and validated the relationships of single-nucleotide polymorphisms (SNPs) on BMP2 , BMP4 , BMPR1A , BMPR1B , and BMPR2 with thicker cIMT by 2 independent case-control studies that used different subject selection methods. Among 200 screened SNPs, 12 on BMPR1B were regarded as candidate genetic markers (P-value 5.0×10sup?4/sup). After combining the discovery and validation studies and adjusting for traditional cardiovascular risk factors, rs4456963*G , rs4235438*T , rs2522530*T , and rs3796433*C showed significant higher odds ratios (ORs) of having thicker cIMT (adjusted ORs: 1.50–1.56; all P-values 2.5×10sup?4/sup). Multivariate analyses showed that rs4456963 and rs3796433 were significantly independent determinants of cIMT thickening. The corresponding multivariate-adjusted ORs for rs4456963*G and rs3796433*C alleles were 1.50 (95% confidence interval (CI): 1.22–1.84) and 1.50 (95% CI: 1.23–1.82), respectively. Interaction between rs4456963 and rs3796433 was evident by the significantly higher OR (8.16, 95% CI: 3.12–21.3) for subjects with the GG - CC genotype. The rs4456963*G and rs3796433*C showed positively linear trends with severity of carotid atherosclerosis. Conclusions: We identified 2 SNPs on BMPR1B showing significantly independent correlations with thicker cIMT. The study provides invaluable evidence supporting that BMPR1B is closely related to carotid atherosclerosis and a potential target for the development of therapeutic agents for atherosclerotic disease.
机译：背景：骨形态发生蛋白（BMP）2和4与动脉粥样硬化的发展有关。但是，尚未建立蛋白质，其主要受体与颈动脉内膜中层厚度（cIMT）（动脉粥样硬化的临床前预测表型）之间的关系。方法和结果：我们通过两项采用不同主题选择方法的独立病例对照研究，筛选并验证了具有较厚cIMT的BMP2，BMP4，BMPR1A，BMPR1B和BMPR2的单核苷酸多态性（SNP）的关系。在200个筛选的SNP中，BMPR1B上的12个被认为是候选遗传标记（P值<5.0×10 ？4 ）。结合发现和验证研究并调整了传统的心血管危险因素后，rs4456963 * G，rs4235438 * T，rs2522530 * T和rs3796433 * C表现出具有较高cIMT的较高比值比（OR）（调整后OR：1.50-1.56 ;所有P值<2.5×10 ？4 ）。多变量分析表明，rs4456963和rs3796433是cIMT增厚的显着独立决定因素。 rs4456963 * G和rs3796433 * C等位基因的相应多元校正OR分别为1.50（95％置信区间（CI）：1.22-1.84）和1.50（95％CI：1.23-1.82）。对于具有GG-CC基因型的受试者，OR445（8.16，95％CI：3.12–21.3）显着更高，这证明了rs4456963和rs3796433之间的相互作用。 rs4456963 * G和rs3796433 * C呈线性线性趋势，并伴有颈动脉粥样硬化的严重程度。结论：我们在BMPR1B上鉴定了2个SNP，它们与较厚的cIMT具有明显的独立相关性。这项研究提供了宝贵的证据，证明BMPR1B与颈动脉粥样硬化密切相关，并且是开发动脉粥样硬化疾病治疗剂的潜在目标。

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