A novel polymorphism in the factor XIII B-subunit (His95Arg): relationship to subunit dissociation and venous thrombosis

Komanasin, Nantarat; Catto, Andrew J.; Futers, T. Simon; Vlieg, Astrid Hylckama; Rosendaal, Frits R.; Ariëns, Robert A. S.

doi:10.1111/j.1538-7836.2005.01624.x

Cited by 62 publications

(73 citation statements)

References 32 publications

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“…This variable site corresponds to F13B His95Arg. 12 The G (Arg) allele is at high frequency in the African samples and was not found among the samples from Asia, where protein allele-2 is known to be rare. 10 A candidate for the molecular basis of protein allele-3 initially proved elusive, as no non-synonymous or 5 0 -UTR polymorphism appeared to correspond to this allele.…”

Section: Resultsmentioning

confidence: 99%

“…The His95Arg site, which differs widely in frequency among worldwide populations and is particularly frequent in populations of African origin, does show signs of functional significance, both in terms of its affinity for the A subunit 12 and genetic susceptibility to thrombosis and MI. 12,13 In addition, each of these lineages is associated with a distinct haplotype (TTAC-Arg and CCGT-His) in the region immediately upstream of exon 1, a region likely to contain regulatory sequences for the F13B gene.…”

Section: Discussionmentioning

confidence: 99%

“…12,13 In addition, each of these lineages is associated with a distinct haplotype (TTAC-Arg and CCGT-His) in the region immediately upstream of exon 1, a region likely to contain regulatory sequences for the F13B gene. Two SNPs (1617 and 1835, Supplementary Table 2) in the upstream region create putative transcription factor-binding sites, approximately 1 kb upstream of the first exon.…”

Section: Discussionmentioning

confidence: 99%

“…Factor XIII activity in samples representing different geographic human populations demonstrated that at least some of the variance was due to the B subunit, despite the fact that it has no known catalytic activity. 11 A later molecular study 12 showed that the 95Arg allele of the B subunit was associated with an increased rate of dissociation of the A 2 B 2 tetramer, a key step in the activation of the enzyme. Casecontrol data from the same study also suggested a role for the F13B 95Arg variant in susceptibility to thrombosis.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the 95Arg variant appears to interact with the 34Leu variant of the A subunit to reduce the risk of nonfatal myocardial infarction (MI) in women undergoing postmenopausal estrogen therapy. 13 The high level of interpopulation differentiation 10 and the suggestion that at least some of the polymorphism at this locus may be functionally significant 11,12 point to the possibility that this locus may have been under the effect of local natural selection. However, a neutral explanation is also possible.…”

Section: Introductionmentioning

confidence: 99%

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Natural selection and the molecular basis of electrophoretic variation at the coagulation F13B locus

et al. 2008

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Electrophoretic analysis of protein variation at the coagulation F13B locus has previously revealed three alleles, with alleles 1, 2, and 3 each being at high frequency in European, African, and Asian populations, respectively. To determine if this unusual pattern of interpopulation differentiation reflects local natural selection or neutral genetic drift, we re-sequenced 4.6 kb of the gene, encompassing all exons, splice junctions, and 1.4 kb of the promoter, in African, European, and Asian samples. These analyses revealed three major lineages, which correspond to the common protein alleles and differ from each other at a nonsynonymous substitution in exon 3 and a novel splice acceptor in intron K. There is previous evidence that these lineages are not functionally equivalent; we therefore carried out case -control analyses and confirmed that variability at F13B modulates susceptibility and/or survivorship in coronary artery disease (Po0.05) and type II diabetes within the coronary artery disease cohort (Po0.01). Tajima's D and Fu and Li's tests did not indicate significant departures from neutral expectations. However, publicly available data from SeattleSNPs and HapMap do indicate highly unusual levels of population differentiation (P ¼ 0.003) and an excess of allele-specific, extended haplotype homozygosity within the African population (P ¼ 0.0125). Possible causes of this putative signal of selection include hematophagous organisms, infection by pathogens that cause disseminated intravascular coagulation, and metabolic or dietary factors.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Natural selection and the molecular basis of electrophoretic variation at the coagulation F13B locus

et al. 2008

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Association of Genetic Variations With Nonfatal Venous Thrombosis in Postmenopausal Women

Smith¹,

Hindorff²,

Heckbert³

et al. 2007

JAMA

181

182

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Context Although the roles of clotting proteins and enzymes that activate or inhibit fibrin production and lysis are well characterized, the underlying contribution of genetic variation in these constituents to risk of venous thrombosis (VT) has not been fully investigated.Objective To describe the association of common genetic variation in 24 coagulation, anticoagulation, fibrinolysis, and antifibrinolysis candidate genes with risk of incident nonfatal VT in postmenopausal women.Design, Setting, and Participants Population-based case-control study conducted in a large integrated health care system in Washington State. Participants were perimenopausal and postmenopausal women aged 30 to 89 years who sustained a first VT event between January 1995 and December 2002 (n=349) and 1680 controls matched on age, hypertension status, and calendar year (n=1680).Main Outcome Measure Risk of venous thrombosis associated with global variation within a gene as measured by common haplotypes and with individual haplotypes and single nucleotide polymorphisms (SNPs). Significance of the associations was assessed by a .20 threshold of the false-discovery rate q value, which accounts for multiple testing. ResultsOnly the tissue factor pathway inhibitor gene demonstrated global association with risk (q = .13). Five significant SNP associations were identified across 3 of the candidate genes (factors V, XI, and protein C) in SNP analyses. Two associations have been previously reported. Another 22 variants across 15 genes had P values less than .05 but q values between .20 and .35. Five of these confirm previously reported associations (fibrinogen genes and protein C), 2 were inconsistent with earlier reports (thrombomodulin and plasminogen activator inhibitor 1), and 15 were new discoveries. ConclusionsAfter accounting for multiple testing, 5 SNPs associated with VT risk were identified, 3 of which have not been previously reported. Replication of these novel associations in other populations is necessary to corroborate these findings and identify which genetic factors may influence VT risk in postmenopausal women.

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A Genome‐Wide Association Study for Venous Thromboembolism: The Extended Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

Tang

Teichert

Chasman

et al. 2013

Genetic Epidemiology

105

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Venous thromboembolism (VTE) is a common, heritable disease resulting in high rates of hospitalization and mortality. Yet few associations between VTE and genetic variants, all in the coagulation pathway, have been established. To identify additional genetic determinants of VTE, we conducted a 2-stage genome-wide association study (GWAS) among individuals of European ancestry in the extended CHARGE VTE consortium. The discovery GWAS comprised 1,618 incident VTE cases out of 44,499 participants from six community-based studies. Genotypes for genome-wide single-nucleotide polymorphisms (SNPs) were imputed to ~2.5 million SNPs in HapMap and association with VTE assessed using study-design appropriate regression methods. Meta-analysis of these results identified two known loci, in F5 and ABO. Top 1,047 tag SNPs (p≤0.0016) from the discovery GWAS were tested for association in an additional 3,231 cases and 3,536 controls from three case-control studies. In the combined data from these two stages, additional genome-wide significant associations were observed on 4q35 at F11 (top SNP rs4253399, intronic to F11) and on 4q28 at FGG (rs6536024, 9.7 kb from FGG) (p<5.0×10−13 for both). The associations at the FGG locus were not completely explained by previously reported variants. Loci at or near SUSD1 and OTUD7A showed borderline yet novel associations (p<5.0×10-6) and constitute new candidate genes. In conclusion, this large GWAS replicated key genetic associations in F5 and ABO, and confirmed the importance of F11 and FGG loci for VTE. Future studies are warranted to better characterize the associations with F11 and FGG and to replicate the new candidate associations.

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A novel polymorphism in the factor XIII B-subunit (His95Arg): relationship to subunit dissociation and venous thrombosis

Cited by 62 publications

References 32 publications

Natural selection and the molecular basis of electrophoretic variation at the coagulation F13B locus

Natural selection and the molecular basis of electrophoretic variation at the coagulation F13B locus

Association of Genetic Variations With Nonfatal Venous Thrombosis in Postmenopausal Women

A Genome‐Wide Association Study for Venous Thromboembolism: The Extended Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

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