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Prevalence of the factor V-Leiden mutation in four distinct American ethnic populations
J P Gregg1, A J Yamane, W W Grody
1Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, California 90095-1732, USA.
Insights
The factor V-Leiden mutation, a common cause of blood clots, is most frequent in Caucasians but also present in Hispanic and African Americans. This genetic mutation is rare in Asian and Native American populations.
Area of Science:
- Genetics
- Hematology
- Epidemiology
Background:
- Activated protein C (APC) resistance is a primary risk factor for venous thromboembolism.
- The factor V-Leiden mutation (Arg 506 to Gln) accounts for over 90% of APC resistance cases.
- This mutation is an autosomal dominant trait with high prevalence in individuals of European Caucasian descent.
Purpose of the Study:
- To investigate the frequency of the factor V-Leiden mutation across diverse ethnic groups.
- To determine the ethnic stratification of this common genetic disorder.
- To inform the development of targeted screening programs for thromboembolism risk.
Main Methods:
- A multiethnic survey of 602 individuals was conducted.
- Genotyping was performed to detect the factor V-Leiden mutation.
- Allele frequencies were analyzed across different ethnic populations including Hispanic-Americans, African-Americans, Asian-Americans, and Native Americans.
Main Results:
- The factor V-Leiden allele frequency was 1.65% in Hispanic-Americans and 0.87% in African-Americans.
- No factor V-Leiden mutations were detected in Asian-Americans or Native Americans.
- The mutation was most frequent in populations with significant Caucasian admixture.
Conclusions:
- The factor V-Leiden mutation exhibits ethnic stratification, being prevalent in Caucasians and present at lower frequencies in Hispanic and African populations.
- The mutation is rare in Asian and Native American groups.
- Understanding this ethnic distribution is crucial for developing cost-effective screening strategies for identifying individuals at risk of venous thromboembolism.
Abstract:
Resistance to activated protein C (APC) is the most common risk factor for venous thromboembolism, a major cause of morbidity and mortality with an incidence of about 1/1,000 per year. The Arg 506 to Gln mutation in exon 10 of the coagulation factor V gene (factor V-Leiden) has been found to be responsible for over 90% of the APC resistance cases and is an autosomal dominant trait. Initial studies have suggested that this mutation is restricted to individuals of European Caucasian extraction with an average allele frequency in European and American Caucasians of 4.4%, making it one of the most common monogenic disorders in the Caucasian population. A limited number of other ethnic populations have been tested and the mutation has been found only rarely. In our multiethnic survey of 602 individuals, Hispanic-Americans had the highest observed frequency of the factor V-Leiden mutant allele, 1.65%, while African-Americans had a somewhat lower frequency, 0.87%. No factor V-Leiden mutations were found in 191 Asian-Americans or 54 Native-Americans tested. These results indicate that the factor V-Leiden mutation segregates in populations with significant Caucasian admixture and is rare in genetically distant non-European groups. This ethnic stratification may be important in developing cost-effective selective screening programs to identify individuals at risk for thromboembolism and offer prophylactic therapy.