Reference

Tormene D et al. Factor V Leiden mutation and risk of venous thromboembolism in pregnant women. Haematologica 2001;86:1305-9.

Category of HuGE information
Specify the types of information (from the list below) available in the article:

1. Prevalence of gene variant
2. Gene-disease association
3. Gene-environment interaction
4. Gene-gene interaction
5. Genetic test evaluation/monitoring

2. Gene-disease association

3. Although the association studied implies a gene-environment interaction (environmental exposure: pregnancy status), no nonpregnant group was studied.

Carrier status for factor V Leiden is associated with increased risk of venous thromboembolism (VTE) during pregnancy or puerperium.

Gene(s)
Identification of the following:

1. Gene name
2. Chromosome location
3. Gene product/function
4. Alleles
5. OMIM #

1. Gene name: F5
2. Chromosome location: 1q23
3. Gene product/function: Factor V Leiden, with increased resistance to activated protein C
4. Alleles: F5, ARG506GLN, 1691G-A (factor V Leiden) F5, R2
5. OMIM #: 227400

Environmental factor(s)
Identification of the major environmental factors studied (infectious, chemical, physical, nutritional, and behavioral)

Pregnancy or postpartum period

Health outcome(s)
Identification of the major health outcome(s) studied

1. Case-control
2. Cohort 
3. Cross-sectional
4. Descriptive or case series
5. Clinical trial
6. Population screening

1. Cohort case definition
2. Exclusion criteria
3. Gender
4. Race/ethnicity
5. Age
6. Time period
7. Geographic location
8. Number of participants

1. Cohort selection criteria: Exposed: carriers for factor V Leiden, among women who were family members of patients who had both factor V Leiden mutation and an objective diagnosis of VTE. Unexposed: noncarriers for factor V Leiden among women who were family members of patients who had both factor V Leiden mutation and an objective diagnosis of VTE.
2. Exclusion criteria: Never pregnant, younger than 15 years of age
3. Gender: Female
4. Race/ethnicity: Not specified
5. Age: 15 years or older
6. Time period: May 1994 to June 2000
7. Geographic location: Padua, Italy
8. Number of participants: 267

1. Environmental factor
2. Exposure assessment
3. Exposure definition
4. Number of participants with exposure data (% of total eligible)

1. Environmental factor:  No environmental factor was directly studied, except that the VTE events had to have occurred during pregnancy or postpartum (within 3 months of childbirth)
2. Exposure assessment: N/A
3. Exposure definition: N/A
4. Number of participants with exposure data: N/A

1. Gene
2. DNA source
3. Methodology
4. Number of participants genotyped (% of total eligible)

1. Gene: Factor V Leiden mutation
2. DNA source: Not specified
3. Methodology: Not reported
4. Number of participants genotyped: Not reported

1. Prevalence of gene variant
2. Gene-disease association
3. Gene-environment interaction
4. Gene-gene interaction
5. Genetic test evaluation

1.  Prevalence of gene variant among the probands’ female family members without the exclusion criteria above was 105/186=56%. 

2.  Gene-disease association:  

Absolute risk of VTE episodes per number of pregnancies:

Absolute risk of VTE episodes per number of women:

Relative risk of VTE comparing women carriers of heterozygous for factor V Leiden to noncarriers: 5.3 (95% CI 0.6-43.9) 

Relative risk of VTE comparing women carriers of double heterozygous defect or homozygous for factor V Leiden to noncarriers: 15.4 (95% CI 1.4-164)

Factor V Leiden is a risk factor for VTE during pregnancy or puerperium. Screening for factor V Leiden mutation may be useful for women of fertile age who are relatives of probands with a history of VTE, because those who screen positive may benefit from thromboprophylaxis during pregnancy and puerperium.

There are several methodological issues.  

1. The study population comprises women who were family members of patients who had both factor V Leiden mutation and a history of VTE. Clearly these subjects had a higher pretest probability of having factor V leiden mutation than a random sample of women of similar age from the general population. The prevalence rate of the genetic defect in this study, therefore, does not have much meaning from a public health standpoint.
2. Similarly, because of the way subjects were selected, the absolute risk of VTE in this sample may be higher than in the general population.
3. Because of their family history of the coagulation defect as well as family history of VTE, these subjects might have been more likely to have VTE diagnosed. This bias, however, should apply to both cases and controls and should not affect the relative risk estimates.
4. The number of VTE episodes was very small. In some subgroups, only one episode was available for analysis, causing very large confidence intervals and greatly limiting any conclusions that could be drawn from this analysis.
5. No baseline comparisons of subject characteristics (e.g., age, number of pregnancies, etc.) between cases and controls were presented. The authors simply state that the two groups were “well matched.” No multivariable analysis was performed. Therefore, potential confounding factors cannot be excluded in these results.