Relational analysis among fibrinogenic Bβ-chain gene polymorphisms and its functional expression and obesity

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.: