海南汉族人群九个纤维蛋白原基因多态性及其与血浆纤维蛋白原水平的关系

目的 调查海南汉族健康人群αTaqⅠ和βBclⅠ、HinfⅠA／C、448G／A、βBsmA ⅠG／C、＋1689T／G、-148C／T、-249C／T、-455G／A多态性的等位基因频率及其与血浆纤维蛋白原（fibrinogen，Fg）水平的关系。方法 用比浊法测定238名健康个体的血浆Fg浓度，用PCR-限制性片段长度多态性方法及测序法分析多态性基因型，并用协方差分析比较9个位点的基因型与血浆Fg水平的关系。结果 海南汉族人群αTaqⅠ、βBclⅠ、HinfⅠA／C、C448、βBsmAⅠG／C、＋1689T／G、-148C／T、-249C／T、-455G／A稀有位点的等位基因频率分别为0．445、0．239、0．134、0．235、0．273、0．241、0．265、0．441、0．254，9个位点之间存在连锁不平衡；在总人群中，-455GA和AA基因型、-148CT和TT基因型、αTaqⅠT1T1基因型组的血浆Fg水平比野生型组高（P值均〈0．01）；在男性人群中，-455GA和AA基因型、-148CT和TT基因型、αTaqⅠT1T1、αTaqⅠT1T2基因型组的血浆Fg水平比野生型组高（P值均〈0．01）。在女性人群中，携带稀有位点A^-455、T^-148、αTaⅠT1的基因型组与野生型组之间的血浆赡水平差异无统计学意义。结论 在9个多态性位点之间存在连锁不平衡；A^-455、T^-148、αTaqⅠT1位点与血浆Fg水平增高关联，β-Fg-455G／A、-148C／T及α-TaqⅠ多态性与男性血浆Fg水平关联。

Nine polymorphisms of fibrinogen gene and their association with plasma fibrinogen levels in Hainan Han population

OBJECTIVE: To investigate the allelic frequencies of polymorphisms of alpha Taq I and beta Bcl I, Hinf I A/C, 448 G/A, beta BsmA I G/C, +1689T/G, -148C/T, -249C/T, -455G/A in Hainan Han population and their association with plasma fibrinogen level. METHODS: Turbidmetric assay was used to measure plasma fibrinogen level of two hundred and thirty-eight healthy individuals. The genotypes were characterized by PCR-RFLP and sequence analysis. The relationships between the genotypes and plasma fibrinogen levels were analyzed by t test and ANOVA. RESULTS: The frequencies of the rare alleles of alpha Taq I and beta Bcl I, Hinf I A/C, 448 G/A, beta BsmA I G/C, +1689T/G, -148C/T, -249C/T, -455G/A polymorphisms were 0.445, 0.239, 0.134, 0.235, 0.273, 0.241, 0.265, 0.441, 0.254 respectively. In the general population, the plasma fibrinogen level is significantly higher in the groups of genotypes -455GA and AA, -148CT and TT, alpha Taq I T1T1 than in the group of wild types(P=0.004, 0.015 and 0.043 respectively). In the men, plasma fibrinogen level is significantly higher in the groups of genotypes -455GA and AA, -148CT and TT, alpha Taq I T1T1, alpha Taq I T1T2 than in the group of wild types(P=0.001, 0.023, 0.003 and 0.032 respectively). In the women, no significant genotype association with plasma fibrinogen level was detected. CONCLUSION: There was linkage disequilibrium between the fibrinogen gene loci. The beta -455G/A beta 448G/A, alpha Fg Taq I polymorphisms were associated with the difference in plasma fibrinogen in men. A(-455), T(-148) and alpha Taq I T1 alleles were associated with higher fibrinogen levels.