Human Longevity and R506Q Factor V Gene Mutation

Faure-Delanef, Laurence; Quéré, Isabelle; Zouali, Habib; Cohen, Daniel

doi:10.1055/s-0038-1657705

Cited by 10 publications

(3 citation statements)

References 3 publications

(3 reference statements)

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“…However, as a matter of fact factor V Leiden carriership has no major effect on the overall life expectancy 69 and is compatible with extreme longevity, being present in centenarian individuals at the same rate (3.9 to 4.0%) than in noncentenarians (2.6 to 5.6%). 22,70…”

Section: Distribution Of Factor V Leiden Mutation In Different Populamentioning

confidence: 99%

Epidemiology of Factor V Leiden: Clinical Implications

Stefano¹,

Chiusolo²,

Paciaroni³

et al. 1998

Semin Thromb Hemost

196

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Inherited resistance to activated protein C (APC) has been recently recognized as a novel cause underlying venous thrombophilia. In most cases APC resistance is due to a single point mutation in the factor V gene leading to a replacement of Arg506 with Gln (factor V Leiden). Factor V Leiden allele is present in about 5% of the Caucasian individuals (Europeans, Jews, Israeli Arabs, and Indians) and is virtually absent in Africans, Asians, and races with Asian ancestry such as Amerindians, Eskimos, and Polynesians; this suggests a single origin of the mutation, which has been proven by haplotype analysis. A low prevalence of the mutation (1%) was noticed in African-Americans for recent racial admixture. Factor V Leiden presents not a major role as risk factor for arterial thrombosis, while it is present in 18% of Caucasian patients with venous thrombosis. This high incidence prevalence mirrors the incidence in the corresponding general populations and can be even higher in some areas according to the ethnic background. Conversely, factor V Leiden is usually not found in non-Caucasian thrombotic patients; this could give reason of the lower incidence of venous thrombotic disease in Africa and Asia in comparison with Europe. Therefore, screening for factor V Leiden is suggested for all Caucasian individuals with previous venous thrombosis; inclusion criteria for the screening should not be stringent because clinical manifestations associated with the mutant genotype can be also mild or secondary to circumstantial risk factors or manifesting at advanced age. Factor V Leiden can act also as concurrent risk factor in individuals with deficiency of natural inhibitors or mild hyperhomocysteinemia. So far, screening for the mutation in individuals with no history of thrombosis is recommended only for relatives of proband patients identified as carriers; the available data do not justify indiscriminate screening before risk situations such as oral contraceptives intake, pregnancy, or high-risk surgery.

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Section: Distribution Of Factor V Leiden Mutation In Different Populamentioning

confidence: 99%

Epidemiology of Factor V Leiden: Clinical Implications

Stefano¹,

Chiusolo²,

Paciaroni³

et al. 1998

Semin Thromb Hemost

196

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“…We decided to exclude patients for whom the diagnosis of venous thromboembolism was ruled out and who had a personal history of venous thromboembolism; we believe those patients were not good controls because they already suffered from venous thromboembolism. Previous studies have suggested that factor V Leiden mutation was not associated either with a reduced life expectancy (24)(25)(26)(27) nor with the occurrence of cardiovascular events (18,28). Could our selection process explain that patients over 70 years with venous thromboembolism had a far lower prevalence of APC resistance?…”

Section: Discussionmentioning

confidence: 88%

Is APC Resistance a Risk Factor for Venous Thromboembolism in Patients over 70 Years?

Lacut¹,

Gal²,

Dreden³

et al. 2002

Thromb Haemost

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SummaryActivated protein C (APC) resistance is the most common risk factor for venous thromboembolism (VTE). Previous studies mostly analysed patients under 70 years and reported a four-to sevenfold increased risk. This case-control study included consecutive patients referred for a clinical suspicion VTE to our medical unit: 621 patients with a well-documented diagnosis (cases) and 406 patients for which the diagnosis was ruled out and who had no personal history of VTE (controls). APC resistance related to factor V Leiden was defined by either a positive DNA analysis or a positive STA® Staclot APC-R assay. Under 70 years, APC resistance was associated with a threefold increased risk of VTE (odds ratio 3.2, 95% CI, 1.7 to 6.0), whereas in patients over 70 years, it appeared to be no longer a strong risk factor (odds ratio 0.8, 95% CI, 0.4 to 1.7). Age appeared as an effectmeasure modifier with a significant interaction (p = 0.005). Our data suggest that APC resistance is not a risk factor for VTE in elderly.

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“…Up to now, at least three single tests (for protein C, protein S, and APC resistance) were used simultaneously to look for defects in this inhibitor system. To simplify this approach, a number of screening tests which claim to recognize all known defects of the protein C pathway have been developed (3)(4)(5)(6)(7). In the present study, a new commercially available assay -Protein C Pathway Test (Gradipore Ltd., North Ryde, Australia) -was evaluated for clinical routine.…”

mentioning

confidence: 99%

Cerebral Vein Thrombosis not Related to Use of Oral Contraceptives in a 7-year-old Child Carrier of the Prothrombin 20210A Allele

Stefano¹,

Paciaroni²,

Chiusolo³

et al. 1999

Thromb Haemost

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102 years, range 100-109) were collected within a period of one year from the General Registry Offices, were ambulatory, self-sufficient, and lived in their homes in metropolitan communities of Northern Italy (Milan, Modena, Genova and the corresponding provinces) (4). Exclusion criteria were infection, inflammation, cancer, dementia, diabetes, renal and liver disease. Healthy individuals (n = 568; 207 males and 361 females, median age 45, range 14-79) were chosen from the general population from the same communities in Northern Italy. Arterial or venous thrombotic disease was excluded on the basis of clinical history and physical examination and using a structured validated questionnaire (4). Genomic DNA was prepared by standard techniques and the prothrombin mutation was detected by allele specific amplification (ASA) (5). There were four heterozygotes (all women) among 125 centenarians (allele frequency 1.6%; 95% CI 0-1.6) and 16 (9 women and 7 men) among 568 controls (allele frequency 1.4%; 95% CI 0.7-2). Allele frequencies (1.6% vs 1.4%) did not differ in the two groups (p = 0.8; odds ratio 1.1:95% CI 0.4-3.5). None of the centenarians studied was homozygous for the G20210A mutation nor had a double defect (factor V G1691A and prothrombin G20210A mutations). Because there was a greater proportion of women among centenarians, 94 female centenarians were compared with 361 female controls. Allele frequencies were not substantially different from those found in the whole population. None of the controls had a double gene defect of factor V and prothrombin mutation. All the four centenarians heterozygous for the prothrombin G20210A mutation had been exposed during their long life to circumstantial thrombotic risk factors such as pregnancy, major surgery, trauma without any antithrombotic prophylaxis and yet they did not develop symptomatic deep venous thrombosis. As previously found for the factor V G1691A mutation (4, 6, 7), the prevalence of the 20210A allele is similar in centenarians and in healthy individuals, indicating that these mutations associated with thrombophilia are compatible with longevity and successful aging.

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Human Longevity and R506Q Factor V Gene Mutation

Cited by 10 publications

References 3 publications

Epidemiology of Factor V Leiden: Clinical Implications

Epidemiology of Factor V Leiden: Clinical Implications

Is APC Resistance a Risk Factor for Venous Thromboembolism in Patients over 70 Years?

Cerebral Vein Thrombosis not Related to Use of Oral Contraceptives in a 7-year-old Child Carrier of the Prothrombin 20210A Allele

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