Factor 11 single-nucleotide variants in women with heavy menstrual bleeding

Autor: Karina Meijer, René Mulder, Sophie Wiewel-Verschueren, Andre B. Mulder
Přispěvatelé: Vascular Ageing Programme (VAP), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Stem Cell Aging Leukemia and Lymphoma (SALL)
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Adult
0301 basic medicine
Excessive Bleeding
VENOUS THROMBOSIS
MISSENSE MUTATIONS
Pathology
medicine.medical_specialty
PARTIAL THROMBOPLASTIN TIME
Factor XI Deficiency
Genome-wide association study
030204 cardiovascular system & hematology
Polymorphism
Single Nucleotide
Gastroenterology
03 medical and health sciences
0302 clinical medicine
Internal medicine
Humans
Medicine
Missense mutation
Clinical significance
DEEP-VEIN THROMBOSIS
GENOME-WIDE ASSOCIATION
skin and connective tissue diseases
Menorrhagia
Factor XI
single-nucleotide variants
RISK
FACTOR-XI DEFICIENCY
medicine.diagnostic_test
business.industry
Heavy menstrual bleeding
Obstetrics and Gynecology
Exons
Middle Aged
medicine.disease
factor XI
BLOOD-COAGULATION FACTOR
Thrombosis
Introns
MOLECULAR-GENETIC ANALYSIS
Venous thrombosis
030104 developmental biology
Case-Control Studies
Female
business
human activities
F11 MUTATIONS
Partial thromboplastin time
Zdroj: Journal of obstetrics and gynaecology, 37(7), 912-918. TAYLOR & FRANCIS INC
ISSN: 0144-3615
Popis: In a previous study it was shown that lower factor XI (FXI) levels in women with heavy menstrual bleeding (HMB). Our aim was to determine the single-nucleotide variants (SNVs) in the F11 gene in women with HMB. In addition, an extensive literature search was performed to determine the clinical significance of each SNV. Patients referred for HMB (PBAC-score100) were included. With direct sequencing analysis of all 15 exons and flanking introns of the F11 gene, 29 different non-structural SNVs were detected in 49 patients with HMB. Interestingly, most of these SNVs have previously been associated with venous thrombosis instead of bleeding. These findings have not helped to elucidate the molecular basis of HMB. They also question the specificity of previously reported F11 variations in patients with thrombosis. More studies are needed to explain the lower FXI levels seen in patients with HMB. IMPACT STATEMENT Women with mild deficiencies of factor XI (FXI) ( 70%) are prone to excessive bleeding during menstruation. Bleeding manifestations are not well correlated with plasma FXI levels and bleeding episodes can vary widely among patients with similar low FXI levels. In a previous study we showed that women with heavy menstrual bleeding (HMB) had normal, but on average, lower levels of FXI than controls. In light of these findings, we performed F11 gene analysis to determine the single-nucleotide variants (SNVs) in women with HMB and performed an extensive literature search to determine the clinical significance of each SNV. By direct sequencing analysis of the F11 gene we found 29 different non-structural SNVs in 49 women with heavy menstrual bleeding. Remarkably, a number of these SNVs have previously been implicated in thrombosis. These findings have not helped to elucidate the molecular basis of lower FXI levels in HMB. They also question the specificity of previously reported F11 variations in patients with thrombosis. More studies are needed to explain the lower FXI levels seen in patients with HMB.
Databáze: OpenAIRE
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