Wartiovaara U, Perola M, Mikkola H, Tötterman K, Savolainen V, Penttilä A, Grant P J, Tikkanen M J, Vartiainen E, Karhunen P J, Peltonen L, Palotie A
Department of Clinical Chemistry and Biomedicine, Helsinki University Central Hospital, Finland.
Atherosclerosis. 1999 Feb;142(2):295-300. doi: 10.1016/s0021-9150(98)00241-x.
Factor XIII is a transglutaminase that crosslinks fibrin in the last steps of the coagulation process. A few polymorphic sites have been identified in this gene, one of them being a point mutation (FXIII Val34Leu), leading to an amino acid change of valine to leucine. Recently, in British patients, FXIII 34Leu allele was suggested to be associated with a decreased incidence of myocardial infarction (MI). PAI-1 4G/4G genotype seemed to lessen the beneficial effect of FXIII 34Leu allele. The aim of our study was to further investigate the possible protective role of the FXIII 34Leu allele against MI and its suggested interaction with the PAI-1 4G/5G polymorphism. We carried out genotype analyses for FXIII Val34Leu using solid-phase minisequencing in two independent Finnish study groups. In our study, the FXIII 34Leu allele was associated with a lower risk of MI (P = 0.009), however, the PAI-1 4G allele showed no interaction with this polymorphism. To establish the population frequency of the FXIII 34Leu allele and to study the possible variations in Finland four DNA pools from different geographical areas of Finland were genotyped. No significant differences in the allele frequencies were observed (21-28%) except in the Eastern Kainuu area (13%), an area with an increased risk of mortality from coronary artery disease (CAD), supporting the results presented above. The association of FXIII 34Leu variant with a lower incidence of myocardial infarction suggests a new role for FXIII in a polygenic thrombotic disease.
因子 XIII 是一种转谷氨酰胺酶，在凝血过程的最后阶段使纤维蛋白交联。该基因已鉴定出一些多态性位点，其中之一是点突变（FXIII Val34Leu），导致缬氨酸变为亮氨酸的氨基酸变化。最近，在英国患者中，FXIII 34Leu 等位基因被认为与心肌梗死（MI）发病率降低有关。PAI-1 4G/4G 基因型似乎减弱了 FXIII 34Leu 等位基因的有益作用。我们研究的目的是进一步调查 FXIII 34Leu 等位基因对心肌梗死可能的保护作用及其与 PAI-1 4G/5G 多态性的相互作用。我们在两个独立的芬兰研究组中使用固相微测序对 FXIII Val34Leu 进行了基因型分析。在我们的研究中，FXIII 34Leu 等位基因与较低的心肌梗死风险相关（P = 0.009），然而，PAI-1 4G 等位基因与该多态性无相互作用。为确定 FXIII 34Leu 等位基因的群体频率并研究芬兰可能的变异情况，对来自芬兰不同地理区域的四个 DNA 池进行了基因分型。除了东部凯努地区（13%），该地区冠心病（CAD）死亡风险增加，未观察到等位基因频率有显著差异（21 - 28%），这支持了上述结果。FXIII 34Leu 变体与较低的心肌梗死发病率相关，提示因子 XIII 在多基因血栓形成疾病中具有新作用。
