Department of Medical Laboratory, The Affiliated Kailuan General Hospital of North China Coal Medical University, Tangshan 063000, Hebei, PR China.
Department of Medical Laboratory, The Affiliated Kailuan General Hospital of North China Coal Medical University, Tangshan 063000, Hebei, PR China.
Obes Res Clin Pract. 2010 Apr-Jun;4(2):e83-e162. doi: 10.1016/j.orcp.2009.12.001.
Recently, there have been a few studies showing the association between obesity and fibrinogen (Fg) gene polymorphisms, but the reasons still do not clear completely. In this research, we studied the relationship among overweight, obesity and -854G/A, -455G/A, -249C/T, -148C/T, 448G/A, Bcl-1G/A gene polymorphisms of Fg β-chain and its functional expression such as plasma Fg concentration and molecule conglomerate function. 1391 subjects of retired aged employees from Kailuan Group were enrolled with medical examination and questionnaire survey, and which were divided into normal weight group (597 cases), overweight group (609 cases), obese group (185 cases) based on body mass index (BMI). Plasma Fg concentration, fibrin monomer polymerized velocity (FMPV), absorbance maximum (Amax) and FMPV/Amax were measured in all subjects. The gene polymorphisms at six sites of Fg β-chain were detected by polymerase chain reaction-restriction fragment length polymorphism. We found that only the frequencies of Bcl-1A allele and its mutated genotypes in overweight group were significantly higher than ones in normal weight group (P < 0.01). The loose linkage disequilibrium was evident between FgβBcl-1G/A and -455G/A, -148C/T polymorphisms. Fg concentration, FMPV, FMPV/Amax of subjects only with β-854 mutated genotype were significantly higher those with wild genotype in three groups (P < 0.01), and FMPV/Amax of subjects with β-455 mutated genotypes and FMPV of ones with β-249 mutated genotypes were yet higher than those with wild genotype in overweight group (P < 0.05). In conclusion, the Fg β-854 site is an important locus regulating plasma Fg concentration and conglomerate functional expression. Only the people with FgβBcl-1 mutated genotype is the genetic susceptible population of overweight with obvious stable phase. This overweight people can enhance plasma fibrinogenic molecular activity expression by activating mutated genotypes of Fgβ-455 and -249. There are different genetic basis and genetic susceptible population between the overweight patients with obvious stable phase and the patients of progressive development to obesity without obvious overweight stable phase.:
最近有一些研究表明肥胖症与纤维蛋白原（Fg）基因多态性之间存在关联，但原因仍不完全清楚。在这项研究中，我们研究了超重、肥胖症与 Fgβ-链的-854G/A、-455G/A、-249C/T、-148C/T、448G/A、Bcl-1G/A 基因多态性及其功能表达（如血浆 Fg 浓度和分子聚集体功能）之间的关系。我们纳入了 1391 名来自开滦集团的退休员工，通过体检和问卷调查进行研究，并根据体重指数（BMI）将他们分为正常体重组（597 例）、超重组（609 例）和肥胖组（185 例）。所有受试者均测量血浆 Fg 浓度、纤维蛋白单体聚合速度（FMPV）、吸光度最大值（Amax）和 FMPV/Amax。通过聚合酶链反应-限制性片段长度多态性检测 Fgβ-链六个位点的基因多态性。我们发现，只有超重组的 Bcl-1A 等位基因及其突变基因型的频率明显高于正常体重组（P<0.01）。Fgβ-Bcl-1G/A 与-455G/A、-148C/T 多态性之间存在明显的连锁不平衡。在三组中，仅具有β-854 突变基因型的受试者的 Fg 浓度、FMPV、FMPV/Amax 显著高于野生基因型（P<0.01），而超重组中具有β-455 突变基因型的受试者的 FMPV 和具有β-249 突变基因型的受试者的 FMPV 仍高于野生基因型（P<0.05）。总之，Fgβ-854 位点是调节血浆 Fg 浓度和聚集体功能表达的重要基因座。只有具有 Fgβ-Bcl-1 突变基因型的人是超重的遗传易感人群，具有明显的稳定阶段。这种超重的人可以通过激活 Fgβ-455 和 -249 的突变基因型来增强血浆纤维蛋白原分子活性的表达。具有明显稳定阶段的超重患者和无明显超重稳定阶段但进展为肥胖的患者之间存在不同的遗传基础和遗传易感人群。
