血尿酸与纤维蛋白原Bβ链7个位点基因多态性及其功能表达的关系

Association of serum uric acid level with polymorphisms of fibrinogen B β-chain gene at sevensites and its functional expression

目的研究尿酸与纤维蛋白原(fibrinogen,Fib)Bβ链-1420G/A、-993C/T、1689T/G、BsmAIG/C、I6I/D、345C/T和HinfIA/C位点的基因多态性及其血浆Fib和聚合功能表达的关系。方法选取开滦集团离退休职工940例,均抽取清晨空腹静脉血测定血生化、尿酸、血浆Fib,以及纤维蛋白单体聚合速率(FMPV)、最大吸光度(Amax)和FMPV/Amax等反映Fib聚合功能的指标,并检测Fib Bβ链7个位点的基因多态性。依据尿酸值将人群分为高尿酸血症组111例和正常尿酸组829例,分析尿酸异常与血浆Fib相关指标的关系。结果高尿酸血症组-1420GG型、-993CC型、1689TT型、BsmAIGG型、HinfIAC+CC型人群FMPV/Amax明显低于正常尿酸组,I6II型、345CC型人群Fib、FMPV、Amax、FMPV/Amax明显低于正常尿酸组(P<0.05);以尿酸为因变量的多元逐步回归分析,依次筛选出男性、VLDL-C、肌酐、体质量指数、尿素、血糖、高血压及FMPV/Amax等指标(P<0.05,P<0.01)。结论高尿酸作为缺血性脑血管病的重要危险因素,并非仅通过影响血浆Fib系统发挥作用,而可能还与高脂血症、血糖异常以及引发的特殊类型慢性炎性反应共同参与其发病的结果。

Objective To study the association of serum uric acid （UA） level,polymorphisms of fi- brinogen （Fib） Bβ-ehain gene at -1420G/A,-993C/T, 1689T/G, BsmAIG/C, I6I/D, 345C/T and HinflA/C,its plasma Fib level and functional expression. Methods Fasting blood samples were taken from 940 retired workers of Kailuan Corporation to measure their serum UA and Fib levels, fibrin monomer polymerized velocity （FMPV）, absorbance maximum （Amax） and FMPV/A Pol- ymorphisms of Fib Bβ-chain gene were detected. The retired workers were divided into high UA group （n=111） and normal UA group （n=829）. Association between abnormal serum UA and Fib levels was analyzed. Results The FMPV/A serum Fib,FMPV and Amax were significantly lower in high UA group with Bβ -1420GG,-993CC, 1689TT,BsmAIGG, HinfIAC＋CC, I6II and 345CC than in normal UA group （P〈0. 05）. Multivariate stepwise regression analysis showed that serum UA was associated with serum VLDL-C, creatinine, urea nitrogen blood glucose levels,BMI,hypertension and FMPV/Amax in males （P〈0.05,P〈0.01）. Conclusion Hyperuricaemia is an important risk factor for ischemic cerebrovascular disease and plays a role in the pathogenesis of hyperlipemia,abnormal blood glucose and chronic inflammatory reactions.