Gender differences of polymorphisms in the TF and TFPI genes, as related to phenotypes in patients with coronary heart disease and type-2 diabetes
Gender differences of polymorphisms in the TF and TFPI genes, as related to phenotypes in patients with coronary heart disease and type-2 diabetes
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DOI：
10.1186/1477-9560-8-7
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发表时间：
2010-01-01
影响因子：
3.1
通讯作者：
Seljeflot, Ingebjorg
中科院分区：
文献类型：
--
作者：
Opstad, Trine B.;Pettersen, Alf Age;Seljeflot, Ingebjorg
背景：组织因子（TF）及其抑制剂组织因子途径抑制剂（TFPI）是凝血过程启动的主要调节因子，在动脉粥样硬化血栓形成中起重要作用。在这项研究中，我们调查了冠心病患者与健康人相比，六种已知的TF和TFPI单核苷酸多态性（snp）的频率。这些基因型和表型（TF、游离TFPI和总抗原）在冠心病人群中进行评估，并特别参考性别和糖尿病。方法：纳入经血管造影证实的冠心病患者（1001例，22%为女性，20%为糖尿病患者）和204例健康对照（28%为女性）。研究的snp分别为：上游5′区的TF- 1812c /T和TF- 603a /G，内含子2区的TF 5466A/G，上游5′区的tpi - 399c /T和tpi - 287t /C，以及内含子7区的tpi - 33t /C。结果：冠心病人群与对照组之间的任何多态性频率无显著差异。在冠心病人群中，TF 5466 A/G SNP在女性中的发生率明显高于男性（p < 0.001）。TF- 1812c /T和TF- 603a /G snp在无2型糖尿病女性中的发生率明显高于糖尿病女性（均p < 0.018），杂合子基因型与TF血浆水平显著低于纯合子基因型（均p < 0.02）。TFPI- 399c /T和TFPI- 33t /C snp分别与较低和较高的TFPI总抗原水平相关（p均< 0.001）。结论：TF和TFPI基因的遗传变异似乎与性别和2型糖尿病有关，并在一定程度上影响其各自的表型。
Background: Tissue factor (TF) and its inhibitor tissue factor pathway inhibitor (TFPI) are the main regulators of the initiation of the coagulation process, important in atherothrombosis. In this study we have investigated the frequency of six known TF and TFPI single nucleotide polymorphisms (SNPs) in CHD patients as compared to healthy individuals. These genotypes and the phenotypes (TF, TFPI free and total antigen) were evaluated with special reference to gender and diabetes in the CHD population.Methods: Patients with angiographically verified CHD (n = 1001; 22% women, 20% diabetics), and 204 healthy controls (28% women), were included. The investigated SNPs were: TF-1812C/T and TF-603A/G in the 5' upstream region, TF 5466A/G in intron 2, TFPI-399C/T and TFPI-287T/C in the 5' upstream region and the TFPI-33T/C in intron 7.Results: No significant differences in frequencies between the CHD population and the controls of any polymorphisms were observed. In the CHD population, the TF 5466 A/G SNP were significantly more frequent in women as compared to men (p < 0.001). The TF-1812C/T and the TF-603A/G SNPs were significantly more frequent in women without type2 diabetes compared to those with diabetes (p < 0.018, both), and the heterozygous genotypes were associated with significantly lower TF plasma levels compared to the homozygous genotypes (p < 0.02, both). The TFPI-399C/T and the TFPI-33T/C SNPs were associated with lower and higher TFPI total antigen levels, respectively (p < 0.001, both).Conclusion: Genetic variations in the TF and TFPI genes seem to be associated with gender and type-2 diabetes, partly affecting their respective phenotypes.