Lam K S, Ma O C, Bourke C, Chan L C, Janus E D
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong.
Diabetologia. 1998 Jul;41(7):760-6. doi: 10.1007/s001250050984.
We studied the effects of genetic and environmental influences on factor VII coagulant activity (VIIc) in Chinese diabetic patients (263 with Type II [non-insulin-dependent] diabetes mellitus, 78 with Type I [insulin-dependent] diabetes mellitus) and 143 normal control subjects. VIIc was measured by a one-stage biological assay. The R/Q353 or Msp1 polymorphism at codon 353 of the factor VII gene was detected after Msp1 digestion of polymerase chain reaction-amplified genomic DNA. In both diabetic and control subjects the allele frequencies of the R (M1) and Q (M2) alleles were 0.96 and 0.04; the corresponding reported frequencies in Caucasians being 0.90 and 0.10: VIIc were 21% lower in Chinese control subjects and Type I diabetic patients with R/Q, compared with R/R subjects (p < 0.001 and p < 0.05). The corresponding difference was 4% for Type II diabetc patients (p = NS). Type II diabetic patients had higher mean VIIc levels than control subjects and Type I diabetic patients (p < 0.01); they were also older, and had higher serum creatinine and triglyceride (all p < 0.01). They also had higher VIIc levels than an age-matched older control group (p < 0.01; n = 182) in whom the genotype effect was clearly seen. On stepwise linear regression analysis, the significant independent determinants of VIIc were serum triglyceride (contributing 20% and 25% to variance in control subjects and diabetic patients), the R/Q353 genotype (contributing to 12% of the variance in control subjects but only 1% in diabetic patients), age and total cholesterol in all subjects, and in the diabetic patients female sex, urinary albumin excretion rate and serum creatinine. VIIc was higher in diabetic patients with macroangiopathy and retinopathy (both p < 0.0001). We conclude that compared with Caucasians, the Q allele frequency is significantly lower in these Chinese subjects. Plasma VIIc is determined by both genetic and environmental influences such that in Chinese Type II diabetic patients, the effect of environmental factors predominates, almost negating the influence of the R/Q353 genotype. High VIIc may contribute to the increased cardiovascular risk in Type II diabetic patients.
我们研究了遗传和环境因素对中国糖尿病患者（263例II型[非胰岛素依赖型]糖尿病患者、78例I型[胰岛素依赖型]糖尿病患者）及143名正常对照者凝血因子VII促凝活性（VIIc）的影响。采用一步生物分析法测定VIIc。通过对聚合酶链反应扩增的基因组DNA进行Msp1酶切，检测凝血因子VII基因第353密码子处的R/Q353或Msp1多态性。在糖尿病患者和对照者中，R（M1）和Q（M2）等位基因的频率分别为0.96和0.04；在白种人中相应报道的频率分别为0.90和0.10：与R/R基因型的中国对照者和I型糖尿病患者相比，R/Q基因型者的VIIc水平分别低21%（p < 0.001和p < 0.05）。II型糖尿病患者的相应差异为4%（p = 无显著性差异）。II型糖尿病患者的平均VIIc水平高于对照者和I型糖尿病患者（p < 0.01）；他们年龄更大，血清肌酐和甘油三酯水平更高（均p < 0.01）。他们的VIIc水平也高于年龄匹配的老年对照组（p < 0.01；n = 182），在该对照组中基因型效应明显可见。逐步线性回归分析显示，VIIc的显著独立决定因素在对照者和糖尿病患者中分别为血清甘油三酯（分别解释变异的20%和25%）、R/Q353基因型（在对照者中解释变异的12%，但在糖尿病患者中仅为1%）、年龄和总胆固醇，在糖尿病患者中还有女性性别、尿白蛋白排泄率和血清肌酐。患有大血管病变和视网膜病变的糖尿病患者的VIIc水平更高（均p < 0.0001）。我们得出结论，与白种人相比，这些中国受试者的Q等位基因频率显著更低。血浆VIIc受遗传和环境因素共同影响，在II型中国糖尿病患者中，环境因素的影响占主导，几乎抵消了R/Q353基因型的影响。高VIIc水平可能导致II型糖尿病患者心血管风险增加。
