doi: 10.1161/hq0202.102874
© 2002 American Heart Association, Inc.
Thrombosis |
Factor XIIIA Val34Leu Polymorphism Does Not Predict Risk of Coronary Heart Disease
The Atherosclerosis Risk in Communities (ARIC) Study
From the Vascular Biology Research Center and Hematology Division (N.A., C.A., Y.-W.W., H.J., K.K.W.), University of Texas-Houston Medical School; the Division of Epidemiology (A.R.F.), School of Public Health, University of Minnesota, Minneapolis; and the Human Genetics Center (E.B.), University of Texas-Houston Health Science Center.
Reprint requests to Dr Kenneth K. Wu, Professor and Director, Division of Hematology, University of Texas-Houston Medical School, 6431 Fannin, MSB 5.016, Houston, TX 77030. E-mail Kenneth.K.Wu{at}uth.tmc.edu
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Abstract |
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Factor XIII catalyzes the cross-linking of fibrin. Cross-sectional studies have suggested that a common polymorphism site at residue 34 of the A subunit of factor XIII (FXIIIA) with a substitution of Leu for Val (FXIIIA Val34Leu) was associated with reduced coronary heart disease (CHD). This association has not been examined in prospective studies. Healthy subjects (n=15 792) were recruited from 4 US communities into the Atherosclerosis Risk in Communities (ARIC) study from 1987 to 1989. They were followed, and incident CHD events were identified and verified. For the present study, we included 423 patients with CHD as cases and 479 noncases. FXIIIA Val34Leu polymorphism was determined by the single-strand conformational polymorphism method. There were no significant differences in the genotype frequencies between cases and noncases. The genotypes showed little association with known CHD risk factors. A weighted proportional hazards regression analysis adjusting for other risk factors confirmed no association of the genotypes with risk of CHD. This prospective study did not provide evidence of a reduced CHD risk for the FXIIIA 34Leu allele.
Key Words: factor XIII • factor XIIIA Val34Leu polymorphism • coronary heart disease
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Introduction |
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Coagulation factor XIII (FXIII) is essential for normal hemostasis. It plays an important role in the final stages of blood coagulation and in the regulation of fibrinolysis. It is composed of a transglutaminase subunit that catalyzes the cross-linking of fibrin monomers during blood clotting.1 These cross-links modify and stabilize the clot structure and increase its resistance to degradation by fibrinolytic proteases. FXIII also crosslinks several other proteins, including
2-antiplasmin, fibronectin, and collagen. Inherited deficiencies of FXIII lead to delayed bleeding after trauma and poor wound healing. FXIII in plasma is a heterotetramer composed of 2 A subunits arranged as a dimer in association with 2 B subunits. The A subunits exhibit the transglutaminase activity after cleavage of an N-terminal activation peptide by thrombin. Previous studies have shown that the A subunit is genetically heterogeneous, and a number of polymorphisms have been identified.2,3 A G-to-T point mutation in codon 34 of the A subunit, causing a change in an amino acid residue (Val to Leu) situated close to the thrombin cleavage site,4,5 has been reported to protect against myocardial infarction (MI)6,7 and deep venous thrombosis.8,9 However, these reported findings are based on cross-sectional clinical studies and may be subject to bias. Association of this polymorphism with risk of coronary heart disease (CHD) has not been reported in prospective studies. The purpose of the present study was to determine whether the A subunit of FXIII (FXIIIA) Val34Leu polymorphism is a risk factor for incident CHD in a prospective follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort.
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Methods |
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Study Population
In 1987 through 1989, the ARIC study recruited a population-based cohort of men and women aged 45 to 64 years from 4 US communities: Forsyth County, NC; Jackson, Miss (blacks only); the northwest suburbs of Minneapolis, Minn; and Washington County, Md. Criteria for inclusion of subjects from the participating communities and relevant epidemiological data have been reported previously.10 A total of 15 792 participants completed a home interview and clinic examination. Ever since the enrollment, the subjects in this cohort have been prospectively followed for the development of CHD and other vascular events. Participants were contacted annually to identify all hospitalizations and deaths. Death certificates and discharges from local hospitals under ARIC surveillance were also reviewed on a continuous basis to detect events occurring to cohort participants.
Ascertainment of Incident CHD Cases and Cohort Random Sample
A case-cohort design11 was used for this nested genetic study in which information on FXIIIA Val34Leu polymorphism was determined only for incident CHD cases and a stratified random sample of the entire ARIC cohort of 15 792 participants. For the present study, we included CHD events occurring between ARIC visit 1 (1987 to 1989) and December 31, 1993. The mean follow-up time was 6.2 years. We defined CHD incidence as (1) a definite or probable MI, (2) a silent MI between examinations as ascertained by ECG, (3) a definite fatal CHD death, or (4) a coronary revascularization. A complete description of the methods that we used to ascertain cases and of our definitions is published elsewhere.12–14 All identified potential clinical events were reviewed and adjudicated by an ARIC morbidity and mortality classification committee using published criteria.12 Coronary revascularization was defined as having hospital procedure codes for coronary bypass graft, coronary angioplasty, or coronary atherectomy.
A stratified random sample of the entire ARIC cohort was selected as a reference group (designated as noncases). The model-fitting procedures account for some cases being so selected into the cohort random sample.15 For the reference cohort, we oversampled participants with thin average carotid intima-media thickness measurements at baseline (<30th percentile) and also stratified the sampling by age and sex. As a result of these varying sampling fractions, we adjusted for the sampling design during analysis.
Participants were excluded if they were neither white nor African American (n=44), had prevalent CHD (or unknown status) at baseline (n=1120), had a history of stroke (n=69) or transient ischemic attack (n=266) at baseline, or had missing sampling or event information (n=2). We also excluded participants with a missing FXIII Val34Leu result because of a missing DNA sample or a failure of polymerase chain reaction amplification (n=95). The final sample size with genotyping contained 902 individuals: 423 incident CHD cases and 479 noncases.
Baseline Measurements
The definitions and methods used for baseline measurements (systolic blood pressure, hypertension, diabetes mellitus, alcohol intake, plasma total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and fibrinogen) have been published elsewhere.16 Venous blood was collected and processed at the baseline examination according to protocols described previously.17 Specimens were sent by overnight courier to the Central Hemostasis Laboratory in Houston, the Lipid and DNA Laboratory in Houston, and the Chemistry Laboratory in Minneapolis, where they were stored at -70°C until assay.
Determination of FXIIIA Genotypes
Genomic DNA was isolated from buffy-coated white blood cells by phenol chloroform and ethanol precipitation. Genotypes of the FXIIIA-34 dimorphism were determined by polymerase chain reaction and single-strand conformational polymorphism analysis with the use of a published primer sequence.18 A 183-bp DNA fragment containing exon 2/intron B was amplified and subjected to single-strand conformational polymorphism analysis. After denaturation, samples were loaded on 10% acrylamide/bis gels and electrophoresed at room temperature for 16 hours at 2-W constant power. Gels were fixed and silver-stained (Pierce). The genotype was classified as homozygous wild type (VV), heterozygous (VL), or homozygous mutant (LL).
Data Analysis
To evaluate the relationship of FXIIIA Val34Leu polymorphism with other variables, some of which may be confounders in this analysis, we used ANCOVA to compute age-, race-, and sex-adjusted mean levels or percentages of the other variables for Val34Val, Val34Leu, and Leu34Leu. We also used ANCOVA to compute age-, race-, and sex-adjusted mean levels or percentage values of study variables for CHD cases versus noncases after appropriate weighting for the stratified case-cohort sampling design. For this descriptive analysis, we treated the sample as a stratified random sample19 (with cases considered 1 stratum and the noncases divided into 8 age/sex/wall thickness strata) and weighted each stratum by the inverse of the sampling fraction. We computed the risk ratios and 95% CIs for the time to the development of CHD by using a weighted proportional hazards regression by Barlow’s method.15 In the weighted proportional hazards regression models, we adjusted FXIIIA Val34Leu estimates for sex, age, race, and other factors related to CHD in this sample: hypertension, diabetes mellitus, total cholesterol, HDL cholesterol, triglycerides, fibrinogen, smoking, and ethanol intake.
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Results |
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The age-, sex-, and race-adjusted prevalences of the 3 FXIIIA-34 genotypes were not significantly different (P>0.8) between incident cases and noncases (Table 1). When these data were analyzed according to ethnic origin, the age- and sex-adjusted prevalences of the 3 FXIIIA-34 genotypes also were not significantly different between incident cases and noncases. There was also no statistically significant difference in the genotype prevalence between whites and African Americans, after adjusting for age, sex, and CHD incidence (Table 1). Comparisons of allele frequencies between cases and noncases for the total group and by ethnic origin showed no significant difference (Table 2). The Val allele frequency was higher in African Americans than in whites, but this difference did not reach statistical significance (Table 2).
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There were higher levels or prevalences of risk factors (hypertension, systolic blood pressure, total cholesterol, total triglycerides, HDL cholesterol, cigarette smoking, and diabetes mellitus; P<0.001 for each) in the cases than in the noncases. The cases were older than the noncases (56.2 versus 53.8 years, respectively; P<0.0001), and the proportion of male cases was greater than the proportion of male noncases (70.8% versus 42.2%, respectively; P<0.0001). The proportion of African Americans was not significantly different between cases and noncases (26.6% versus 25.1%, respectively; P=0.7). Of our incident cases, 69.5% had an acute coronary syndrome; the remaining 30.5% had silent MI or coronary revascularization. When the nonacute events were excluded from analysis, the difference in FXIIIA Val34Leu alleles between cases and noncases remained statistically insignificant.
Table 3 shows the characteristics of the cohort reference subjects with respect to the presence or absence of Val34Leu polymorphism. FXIIIA Val34Leu genotypes were generally not associated with CHD risk factors except for hypertension and total cholesterol. The participants with the Leu34Leu (LL) genotype had a higher prevalence of hypertension (P=0.014) and lower total cholesterol (P=0.043). There was no significant association between Val34Leu genotypes and plasma fibrinogen levels as was previously shown in another study.6
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The weighted proportional hazards regression analysis showed that the Val34Leu genotype was not significantly associated with the time to the development of CHD, after controlling for potential confounding effects of age, sex, ethnic origin, hypertension, diabetes mellitus, total cholesterol, total triglycerides, HDL cholesterol, fibrinogen, alcohol intake, and smoking. The risk ratios of developing CHD for the FXIIIA Leu34Leu, Val34Leu, and Val34Val genotypes were 1.0, 0.86 (P=0.75), and 1.04 (P=0.92), respectively. From this population-based prospective study, there is no evidence of an association of coagulation FXIIIA Val34Leu polymorphism with the development of CHD.
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Discussion |
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We found no decrease in the risk of incident CHD in individuals heterozygous or homozygous for the FXIIIA Leu34 allele in our community-based, prospective, case-cohort study contrasted with the positive association reported in a small number of studies based on retrospective analyses of small numbers of patients. A cross-sectional study by Kohler et al6 suggested that the 34Leu allele was significantly inversely correlated with MI. The prevalence of this allele was lower in 197 white patients with MI than in 201 patients without MI or in 196 healthy subjects. They also showed that among 3 polymorphisms in the coding region of the A-subunit gene of FXIII, only FXIIIA Val34Leu was associated with coronary artery disease in 275 consecutive patients admitted for angiography.20 They further suggested that the association of FXIIIA 34Leu with CHD became insignificant when the plasminogen activator inhibitor-1 (PAI-1) level was high or when insulin resistance was present.6,21 Another cross-sectional study also showed that the 34Leu allele was associated with a lower risk of MI in a small sample of Finnish men.7 The former study6 found that adjustment for the PAI-1 4G/4G genotype lessened the association of FXIIIA 34Leu allele with CHD, whereas in the latter study,7 the PAI-1 4G allele showed no influence on the association of this polymorphism with CHD. Both studies were not prospective and not population-based and, therefore, potentially subject to bias toward an association between FXIIIA Val34Leu genotype and MI. A recent case-control study reported a null association of Val34Leu with acute coronary syndromes22 in 101 Spanish patients, aged 34 to 85 years. In addition, that study found no association of Val34Leu with acute cerebrovascular events or deep venous thrombosis. In another study, FXIIIA Val34Leu was found not to be associated with thromboangiitis obliterans in 28 patients.23 In our population-based, prospective, case-cohort study, the results did not show an association between FXIIIA Val34Leu polymorphism and incident CHD. Weighted proportional hazards regression analysis failed to show a significant reduction in CHD risk for the Leu allele. In fact, the risk ratios for all 3 genotypes were equivalent. The difference in prevalence rates of FXIII Val34Leu genotype between CHD cases and noncases was negligible (35.2% versus 34.3%, respectively) in our prospective case-cohort study. This negligible difference is confirmed by the fact that there is <10% power to detect significant difference in the prevalence of Val34Leu (VL) genotype between CHD cases and noncases. Our findings do not support a reduction in CHD risk by a Val-to-Leu substitution at residue 34 of the FXIIIA subunit.
It has been shown that the Leu substitution contributes to an increased FXIII activity.10,24,25 The expression of Leu versus Val FXIIIA protein in yeast confirmed a higher transglutaminase activity associated with the Leu allele.26 Its expression in COS cells showed an increased rate of fibrin stabilization, although the specific activity of the fully activated wild-type and Val34Leu mutant did not differ.27 These results would mean that the Leu allele yields more cross-linked fibrin in the thrombi. It is difficult to explain why this allele should be associated with a lower risk of CHD, as reported by previous studies. It was argued that a higher XIII activity conferred by the Leu allele might be expected to contribute to a higher CHD risk by increasing the clot resistance to fibrinolytic lysis.28 It should be noted that FXIII activity in the study subjects was measured by an assay with a high degree of variability. It was also reported that there is a wide range of FXIII activity among healthy subjects.29 Balogh et al29 showed that neither the plasma level nor the specific activity of fully activated purified plasma FXIII was influenced by the presence of the Leu34 allele. Furthermore, FXIII protein levels and activities are influenced by conditions such as inflammation. Saha et al30 showed that racial and genetic components play a significant role in plasma FXIII activity in Asian Indians and Chinese, with Asian Indians having 
33% higher plasma FXIII activity than the Chinese; consequently, plasma FXIII activity may affect the quantitative risk of CHD. The heritability of FXIII activity was the highest (82%) among 10 key hemostatic factors investigated in 501 white female twin pairs aged 18 to 79 years,31 indicating the importance of further research in the genetic regulation of hemostatic factors and atherothrombotic disorders. However, because FXIII activity is one that is sensitive to the polymorphism, it might be expected that the in vitro FXIII activity would be heritable and, therefore, would not provide general information about FXIII heritability. A more general measure of heritability of FXIII may be provided by the antigen rather than the activity data. Additional studies are needed to determine FXIII genetic polymorphisms, FXIII antigen/activity, and the risk of CHD in human subjects.
The Leu allele frequency is highly variable among different races and ethnic groups. It has been reported to be 0.24 to 0.30 in whites, 0.21 to 0.28 in Finns (with the exception of 1 eastern region, where it was 0.13), 0.01 to 013 in Asians, 0.40 in Pima Indians, and 0.14 and 0.18 in Brazilian and African blacks, respectively.7,32,33 The allele frequency in African Americans has not previously been reported. In the present study, we found that the frequency of the Leu allele in African Americans recruited from 2 US communities (Jackson, Mississippi, and Forsyth County, NC) was not significantly different from that in American whites (0.19 versus 0.22, respectively), and the frequency was close to that of African blacks. There was no significant association of Val34Leu with CHD in African Americans or in whites. To our knowledge, this is the first report concerning FXIIIA Val34Leu frequency and its relation to CHD in African Americans.
The FXIIIA Val34Leu polymorphism was not associated with known CHD risk factors, except for hypertension and total cholesterol. The 34Leu allele was associated with a higher percentage of hypertension and lower total cholesterol. There is no obvious reason for this, and these associations did not have an apparent impact on the relationship between the genotypes and the risk of CHD. Most probably, a significant association between the Leu34Leu genotype and risk factors such as hypertension and total cholesterol may be due to chance, considering the small sample size (n=29) in the Leu34Leu genotype.
The present study has several advantages over the cross-sectional case-control studies in that it is population-based and prospective and contains a relatively large number of participants and incident events. The case-cohort model used in the present study is more reliable than the cross-sectional studies used previously, because the controls were not selected but rather represent a stratified random sample of the ARIC cohort. A limitation of the present study is the inclusion of subjects who were aged only 45 to 64 years at the entry into the study. If Val34Leu, like other genetic factors, were to play a more important role in CHD risk in younger subjects, we might have missed individuals dying young or having premature CHD. In addition, the mixed ethnic makeup of the present study population, as opposed to studies in Europe, might have lessened the ability to detect an association of Val34Leu with MI. Therefore, the generalization of results from this population-based, prospective, follow-up study should be limited to middle-aged men and women only.
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Acknowledgments |
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The work was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health contracts N01-HC-55015, -55016, -55018, -55019, -55020, -55021, and -55022. The authors thank the staff and participants in the ARIC study for their important contributions.
Received July 18, 2001; accepted November 12, 2001.
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References |
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1. Muszbek L, Adany R, Mikkola H. Novel aspects of blood coagulation factor XIII, I: structure, distribution, activation, and function. Crit Rev Clin Lab Sci. 1996; 33: 357–421.[Medline] [Order article via Infotrieve]
2. Suzuki 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: 129–135.[Medline] [Order article via Infotrieve]
3. Board PG. Genetic polymorphism of the A subunit of human coagulation factor XIII. Am J Hum Genet. 1979; 31: 116–124.[Medline] [Order article via Infotrieve]
4. Anwar R, Stewart AD, Miloszewski KJA, Losowsky MS. Molecular basis of inherited factor XIII deficiency: identification of multiple mutations provides insights into protein function. Br J Haematol. 1995; 91: 728–735.[Medline] [Order article via Infotrieve]
5.
Mikkola H, Syrjala M, Rasi V, Vahtera E, Hamalainen E, Peltonen L, Palotie A. Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels. Blood. 1994; 84: 517–525.
6. Kohler HP, Stickland MH, Ossei-Gerning N, Carter A, Mikkola H, Grant PJ. Association of a common polymorphism in the factor XIII gene with myocardial infarction. Thromb Haemost. 1998; 79: 8–13.[Medline] [Order article via Infotrieve]
7. Wartiovaara U, Perola M, Mikkola H, Totterman K, Savolainen V, Penttila A, Grant PJ, Tikkanen MJ, Vartiainen E, Karhunen PJ, et al. Association of FXIII Val34Leu with decreased risk of myocardial infarction in Finish males. Atherosclerosis. 1999; 142: 295–300.[CrossRef][Medline] [Order article via Infotrieve]
8.
Catto AJ, Kohler HP, Coore J, Mansfield MW, Stickland MH, Grant PJ. Association of a common polymorphism in the factor XIII gene with venous thrombosis. Blood. 1999; 93: 906–908.
9. Franco RF, Reitsma PH, Lourenco D, Maffei FH, Morelli V, Tavella MH, Araujo AG, Piccinato CE, Zago MA. Factor XIII Val34Leu is a genetic factor involved in the aetiology of venous thrombosis. Thromb Haemost. 1999; 81: 676–679.[Medline] [Order article via Infotrieve]
10.
The ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC) study: design and objectives. Am J Epidemiol. 1989; 129: 687–702.
11.
Prentice RL. A case-cohort design for epidemiological cohort studies and disease prevention trials. Biometrika. 1986; 73: 1–11.
12. White AD, Folsom AR, Chambless LE, Sharrett AR, Yang K, Conwill D, Higgins M, Williams OD, Tyroler HA. Community surveillance of coronary heart disease in the Atherosclerosis Risk in Communities (ARIC) Study: methods and initial two years experience. J Clin Epidemiol. 1996; 49: 223–233.[CrossRef][Medline] [Order article via Infotrieve]
13.
Rosamond WD, Chambless LE, Folsom AR, Cooper LS, Conwill DE, Clegg L, Wang CH, Heiss G. Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med. 1998; 339: 861–867.
14.
Folsom AR, Wu KK, Rosamond WD, Sharrett AR, Chambless LE. Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 1997; 96: 1102–1108.
15. Barlow WE. Robust variance estimation for the case-cohort design. Biometrics. 1994; 50: 1064–1072.[CrossRef][Medline] [Order article via Infotrieve]
16.
Folsom AR, Nieto FJ, McGovern PG, Tsai MY, Malinow MR, Eckfeldt JH, Hess DL, Davis PE. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 1998; 98: 204–210.
17. Papp AC, Hatzakis H, Bracey A, Wu KK. ARIC hemostasis study, I: development of a blood collection and processing system suitable for multicenter hemostatic studies. Thromb Haemost. 1989; 61: 15–19.[Medline] [Order article via Infotrieve]
18. Kohler HP, Ariens RAS, Whitaker P, Grant PJ. A common coding polymorphism in the FXIII A-subunit gene (FXIIIVal34Leu) affects cross-linking activity. Thromb Haemost. 1998; 80: 704.[Medline] [Order article via Infotrieve]
19. Cochran WG. Sampling Techniques. 3rd ed. New York, NY: John Wiley & Sons; 1977.
20. Kohler HP, Futers TS, Grant PJ. Prevalence of three common polymorphisms in the A-subunit gene of factor XIII in patients with coronary artery disease. Thromb Haemost. 1999; 81: 511–515.[Medline] [Order article via Infotrieve]
21. Kohler HP, Grant PJ. Clustering of haemostatic risk factors with FXIIIVal34Leu in patients with myocardial infarction. Thromb Haemost. 1998; 80: 862.[Medline] [Order article via Infotrieve]
22.
Corral J, Gonzales-Conejero R, Iniesta JA, Rivera J, Martinez C, Vicente V. The FXIII Val34Leu polymorphism in venous and arterial thromboembolism. Haematologica. 2000; 85: 293–297.
23. Brodmann M, Renner W, Stark G, Winkler M, Pabst E, Hofmann C, Pilger E. Prothrombotic risk factors in patients with thromboangiitis obliterans. Thromb Res. 2000; 99: 483–486.[CrossRef][Medline] [Order article via Infotrieve]
24.
Anwar R, Gallivan L, Edmonds SD, Markham F. Genotype/phenotype correlations for coagulation factor XIII: specific normal polymorphisms are associated with high or low factor XIII specific activity. Blood. 1999; 93: 897–905.
25.
Ariens RA, Philippou H, Nagaswami C, Weisel JW, Lane DA, Grant PJ. The factor XIII V34L polymorphism accelerates thrombin activation of factor XIII and affects cross-linked fibrin structure. Blood. 2000; 96: 988–995.
26.
Kangsadalampai S, Board PG. The Val34Leu polymorphism in the A subunit of coagulation factor XIII contributes to the large normal range in activity and demonstrates that the activation peptide plays a role in catalytic activity. Blood. 1998; 92: 2766–2770.
27. Wartiovaara U, Mikkola H, Szoke G, Haramura G, Karpati L, Balogh I, Lassila R, Muszbek L, Palotie A. Effect of Val34Leu polymorphism on the activation of the coagulation factor XIIIA. Thromb Haemost. 2000; 84: 591–601.[Medline] [Order article via Infotrieve]
28.
Reed GL, Houng AK. The contribution of activated factor XIII to fibrinolytic resistance in experimental pulmonary embolism. Circulation. 1999; 99: 299–304.
29.
Balogh I, Szoke G, Karpati L, Wartiovaara U, Katona E, Komaromi I, Haramura G, Pfliegler G, Mikkola H, Muszbek L. Val34Leu polymorphism of plasma factor XIII: biochemistry and epidemiology in familial thrombophilia. Blood. 2000; 96: 2479–2486.
30. Saha N, Aston CE, Low PS, Kamboh MI. Racial and genetic determinants of plasma factor XIII activity. Genet Epidemiol. 2000; 19: 440–455.[CrossRef][Medline] [Order article via Infotrieve]
31. De Lange M, Snieder H, Ariens RA, Spector TD, Grant PJ. The genetics of hemostasis: a twin study. Lancet. 2001; 357: 101–105.[CrossRef][Medline] [Order article via Infotrieve]
32. McCormack LJ, Kain K, Catto AJ, Kohler HP, Stickland MH, Grant PJ. Prevalence of FXIII V34L in populations with different cardiovascular risk. Thromb Haemost. 1998; 80: 523–524.[Medline] [Order article via Infotrieve]
33. Attie-Castro FA, Zago MA, Lavinha J, Elion J, Rodrigues-Delfin L, Guerreiro JF, Franco RF. Ethnic heterogeneity of the factor XIII Val34Leu polymorphism. Thromb Haemost. 2000; 84: 601–603.[Medline] [Order article via Infotrieve]
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