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No Val34Leu polymorphism of the gene for factor XIIIA subunit was detected by ARMS-RACE method in three Asian populations

2003; Elsevier BV; Volume: 1; Issue: 8 Linguagem: Inglês

10.1046/j.1538-7836.2003.00339.x

1538-7933

T. Okumura, Tōru Yamada, Sangwoo Park, Akitada Ichinose,

Iron Metabolism and Disorders

Dear Sir, During the course of studies to find genetic defects of XIIIA or XIIIB deficiency, a G→T substitution was identified at codon 34 in exon II of the XIIIA gene (Val34Leu), and turned out to belong to common polymorphisms of the XIIIA gene. Recently, the Val34Leu polymorphism was found to be inversely associated with thrombotic phenotypes, primarily in Caucasians [1Kohler H.P. Futers T.S. Grant P.J. Prevalence of three common polymorphisms in the A-subunit gene of factor XIII in patients with coronary artery disease.Thromb Haemost. 1999; 81: 511-5Crossref PubMed Scopus (0) Google Scholar, 2Elbaz A. Poirier O. Canaple S. Chedru F. Cambien F. Amarenco P. The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction.Blood. 2000; 95: 586-91Crossref PubMed Google Scholar, 3Catto A.J. Kohler H.P. Coore J. Mansfield M.W. Stickland M.H. Grant P.J. Association of a common polymorphism in the factor XIII gene with venous thrombosis.Blood. 1999; 93: 906-8Crossref PubMed Google Scholar]. In contrast to the high prevalence of this polymorphism in Caucasians, a low prevalence has been reported in investigation of a limited number of Japanese subjects [4Suzuki K. Iwata M. Ito S. Matsui K. Uchida A. Mizoi Y. Molecular basis for subtypic differences of the 'a' subunit of coagulation factor XIII with description of the genesis of the subtypes.Hum Genet. 1994; 94: 129-35Crossref PubMed Google Scholar, 5Attie-Castro F.A. Zago M.A. Lavinha J. Elion J. Rodriguez-Delfin L. Guerreiro J.F. Franco R.F. Ethnic heterogeneity of the factor XIII Val34Leu polymorphism.Thromb Haemost. 2000; 84: 601-3Crossref PubMed Google Scholar]. Moreover, to our knowledge the prevalence of this polymorphism has not been determined in Asian populations besides Japanese. To allow the simple and reliable determination of the Val34Leu polymorphism in larger studies, we developed a new genetic diagnostic method by combining an amplification refractory mutation system (ARMS) with rapid automated capillary electrophoresis (RACE) [6Ooe A. Kida M. Yamazaki T. Park S.C. Hamaguchi H. Girolami A. Ichinose A. Common mutation of plasminogen detected in three Asian populations by an amplification refractory mutation system and rapid automated capillary electrophoresis.Thromb Haemost. 1999; 82: 1342-6Crossref PubMed Scopus (17) Google Scholar], and applied it to about 500 Asian subjects including healthy Japanese, Korean, Chinese and Italian individuals, and Japanese patients with ischemic heart disease, cerebrovascular dementia, or Alzheimer's disease. To determine genotypes by ARMS, two differently fluorescence-labeled sense primers, 20 mer with FAM for the Val34 allele (5′-CACAGTGGAGCTTCAGAGCG-3′) and 22 mer with TET for the Leu34 allele (5′-CCCACAGTGGAGCTTCAGAGCT-3′), and a common antisense primer (5′-CTGGACCCAGAGTGGTGG-3′) were used for polymerase chain reaction. Amplified products were analyzed by RACE using an ABI PRISM 310 Genetic Analyzer (Perkin-Elmer, Foster City, CA, USA), as described previously [6Ooe A. Kida M. Yamazaki T. Park S.C. Hamaguchi H. Girolami A. Ichinose A. Common mutation of plasminogen detected in three Asian populations by an amplification refractory mutation system and rapid automated capillary electrophoresis.Thromb Haemost. 1999; 82: 1342-6Crossref PubMed Scopus (17) Google Scholar]. The application of the ARMS-RACE method to 103 healthy Japanese revealed that none had the Val34Leu polymorphism, though its gene frequency was high in Italians (Table 1). This was also true when 201 Japanese patients with ischemic heart disease, cerebrovascular dementia, or Alzheimer's disease were examined. Among the 304 Japanese subjects in this study, the Val34Leu polymorphism was not detected at all, which is inconsistent with the two previous reports that it was found in one out of 46 and one out of 40 Japanese individuals [4Suzuki K. Iwata M. Ito S. Matsui K. Uchida A. Mizoi Y. Molecular basis for subtypic differences of the 'a' subunit of coagulation factor XIII with description of the genesis of the subtypes.Hum Genet. 1994; 94: 129-35Crossref PubMed Google Scholar, 5Attie-Castro F.A. Zago M.A. Lavinha J. Elion J. Rodriguez-Delfin L. Guerreiro J.F. Franco R.F. Ethnic heterogeneity of the factor XIII Val34Leu polymorphism.Thromb Haemost. 2000; 84: 601-3Crossref PubMed Google Scholar]. The reason for this discrepancy is currently unclear; however, the presence of the polymorphism in Suzuki's study could be an error, since it was judged by a mobility shift in single-strand conformation polymorphism analysis. It is also possible that the subjects of the latter study [5Attie-Castro F.A. Zago M.A. Lavinha J. Elion J. Rodriguez-Delfin L. Guerreiro J.F. Franco R.F. Ethnic heterogeneity of the factor XIII Val34Leu polymorphism.Thromb Haemost. 2000; 84: 601-3Crossref PubMed Google Scholar] may not be pure Japanese, since they were 'Japanese descendents' in Brazil and may have been admixed with other ethnic groups having high gene frequencies of the polymorphism.Table 1Prevalence of XIIIA Val34Leu genotypesEthnic groupTotalVal/ValVal/LeuLeu/LeuFrequency*Gene frequency of Leu allele.ControlJapanese103103000.00**P < 0.005 against Italian control subjects.Chinese9595000.00**P < 0.005 against Italian control subjects.Korean100100000.00**P < 0.005 against Italian control subjects.Italian75423030.24Patients (Japanese)Ischemic heart disease8787000.00**P < 0.005 against Italian control subjects.Cerebrovascular dementia2020000.00**P < 0.005 against Italian control subjects.Alzheimer's disease9494000.00**P < 0.005 against Italian control subjects.* Gene frequency of Leu allele.** P < 0.005 against Italian control subjects. Open table in a new tab It was of note that the polymorphism was detected neither in 100 Korean nor in 95 Chinese individuals. Although a total of 499 subjects were examined, the Val34Leu polymorphism was not detected in three Asian populations. In contrast, much higher distribution of the Val34Leu allele has been reported in 160 and 191 Asian subjects in the UK [7McCormack L.J. Kain K. Catto A.J. Kohler H.P. Stickland M.H. Grant P.J. Prevalence of FXIII V34L in populations with different cardiovascular risk [letter].Thromb Haemost. 1998; 80: 523-4Crossref PubMed Scopus (0) Google Scholar, 8Warner D. Mansfield M.W. Grant P.J. Coagulation factor XIII and cardiovascular disease in UK Asian patients undergoing coronary angiography.Thromb Haemost. 2001; 85: 408-11Crossref PubMed Google Scholar]. However, these were Asian Indian in the former study, and originated from India, Pakistan, or Bangladesh in the latter study; therefore, they must be Caucasoid. The Val34Leu polymorphism may have appeared after the Caucasoid–Mongoloid diversion. This is less likely, however, because the Val34Leu allele has also been found to occur frequently in American Indians and Africans [5Attie-Castro F.A. Zago M.A. Lavinha J. Elion J. Rodriguez-Delfin L. Guerreiro J.F. Franco R.F. Ethnic heterogeneity of the factor XIII Val34Leu polymorphism.Thromb Haemost. 2000; 84: 601-3Crossref PubMed Google Scholar]. It is more likely therefore that individuals having only the Val34 allele were ancestors of the three Asian populations. Alternatively, codon 34 of the XIIIA gene may be a hotspot for mutation, and the G→T transversion may have occurred more than once in the other ethnic groups. Since the Val34Leu polymorphism is inversely associated with myocardial infarction, cerebral infarction, and venous thrombosis in Caucasians [1Kohler H.P. Futers T.S. Grant P.J. Prevalence of three common polymorphisms in the A-subunit gene of factor XIII in patients with coronary artery disease.Thromb Haemost. 1999; 81: 511-5Crossref PubMed Scopus (0) Google Scholar, 2Elbaz A. Poirier O. Canaple S. Chedru F. Cambien F. Amarenco P. The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction.Blood. 2000; 95: 586-91Crossref PubMed Google Scholar, 3Catto A.J. Kohler H.P. Coore J. Mansfield M.W. Stickland M.H. Grant P.J. Association of a common polymorphism in the factor XIII gene with venous thrombosis.Blood. 1999; 93: 906-8Crossref PubMed Google Scholar], it is important to study the genuine prevalence of the Val34Leu polymorphism among different ethnic groups. The polymorphism was absent in Japanese individuals both with and without thrombosis. Thus, this polymorphism is not a discriminative risk factor for thrombosis, at least among Japanese. Furthermore, the incidence of thrombosis among Japanese is lower than in Americans (Caucasian) [9Murata M. Genetic polymorphisms associated with thrombotic disorders in the Japanese population.Fibrinol Proteol. 2000; 14: 155-64Crossref Google Scholar]. Since thrombosis is a multifactorial disease, the absence of other genetic risk factors, such as the factor V Leiden and prothrombin G20210A polymorphisms, may compensate for the prothrombotic phenotype of the Val34 allele in Japanese (and also in Korean and Chinese). The prevalence or frequency of each gene polymorphism is quite different between ethnic groups, as is the case with the Ala601Thr variant, a common single nucleotide polymorphism (SNP) of the plasminogen gene in Asian populations alone, including Japanese, Korean, and Chinese [6Ooe A. Kida M. Yamazaki T. Park S.C. Hamaguchi H. Girolami A. Ichinose A. Common mutation of plasminogen detected in three Asian populations by an amplification refractory mutation system and rapid automated capillary electrophoresis.Thromb Haemost. 1999; 82: 1342-6Crossref PubMed Scopus (17) Google Scholar]. Thus, the Val34Leu polymorphism is yet another example of the ethnic specificity of gene polymorphisms. It is important to accumulate data on SNPs of thrombosis-related genes in each ethnic group in order to understand fully these groups' genetic risk factors for thrombosis. This study was supported in part by research grants from the Ministry of Education, Science and Culture, Japan (11470205, 11770071), the Ministry of Health and Welfare (Japan), the Japanese Society for Science Promotion, the Uehara Memorial Foundation (Japan), the Nippon Foundation (Japan), and the KOSEF for Korea-Japan Basic Scientific Promotion Program.