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“The findings and conclusions in this e-journal are those of the author(s) and do not necessarily represent the views of the funding agency.”

The ACE D/D Genotype is Protective Against the Development of
Idiopathic Deep Vein Thrombosis and Pulmonary Embolism

April 8, 2004

Reviewed by:
Krista Yorita
Rollins School of Public Health
Emory University

 

The Health Outcome

Idiopathic deep vein thrombosis (DVT) and pulmonary embolism (PE) are becoming more widely recognized as a public health problem. In particular, the media has brought the cases of DVT and PE caused by long-distance air travel into the public eye (although they represent a small minority of the total cases). Thrombophilias are a current issue in primary care, particularly for the elderly and those who are not ambulatory (1). It is thought that the ACE gene, which codes for angiotensin converting enzyme, may be implicated in the development of thrombophilias, although the mechanism is unknown. The reasoning behind this theory is that angiotensin is involved in the constriction of blood vessels, making clots more likely to lodge and block blood flow (2). The ACE D/D genotype is associated with higher plasma ACE levels, suggesting that it could increase susceptibility to thrombophilia. The authors of this paper cited six other studies looking at this possible relationship, which found associations ranging from 0.64 (protective) to 11.7 (risk factor).


The Finding

This subject group was comprised of 300 cases and 300 controls, evenly distributed among males and females, and of whom 97% were Caucasian. Cases were matched by age, sex, and ethnicity to friends who acted as controls. Whole blood samples were taken from 290 subjects from each group. The study used agarose gel separation of PCR amplified DNA to assess the prevalence of the D/D genotype, which was found in 25.3% of cases and 32.4% of controls.

The main conclusion is that the ACE D/D genotype, representing a homozygous deletion in the intron of interest, may have a slight protective effect (OR= 0.66) against idiopathic DVT and PE. The study also confirmed earlier findings that the Factor V Leiden and Prothrombin G20210A genotypes are strongly associated with thrombophilias. They used logistic regression modeling to determine that two environmental factors-smoking and BMI-were also significant predictors of thrombophilia, when matching for age, gender and ethnicity. None of the genetic factors, when adjusted for, affected the effect of ACE D/D.

Public Health Implications

Although this particular paper found the D/D genotype to have a protective effect, previous studies have reached different conclusions (2-4); reasons for this discrepancy could be due to differences in case definitions, methods for matching cases with controls, environmental and genetic factors controlled for, and target populations. Also, the ethnically homogeneous population in this study makes it impossible to extrapolate the results to other groups.

The public health utility of this study is not clear. First, the reported effect was not large; the protective effect was 0.66, and findings in other studies are inconsistent. Furthermore, the findings contradict the a priori hypothesis that ACE D/D would lead to elevated plasma ACE and increased risk of VTE. However, research on genetic susceptibility to thrombophilia is important and should be continued because this condition presents a significant burden in terms of prevalence and costs-of hospitalization, treatment, and prophylaxis.

References

  1. Lu Y, Hui R, Zhao Y. Factor V Leiden (G1691A) and prothrombin gene G20210A mutations as potential risk factors for venous thromboembolism after total hip or total knee replacement surgery. Thromb Haemost 2002 87(4) 580-5
  2. Jackson A, Brown K, Langdown J. et.al. Effect of the angiotensin-converting enzyme gene deletion polymorphism on the risk of venous thromboembolism. Br J Haematol 2000 111(2) 562-564
  3. Fatini C, Gensini F, Sticchi E. et.al. ACE DD genotype: an independent predisposition factor to venous thromboembolism. Eur J Clin Invest 2003 33(8) 642-7
  4. Insertion/deletion polymorphsim of the angiotensin I converting enzyme gene and pulmonary thromboembolism in Chinese population. Zhonghua Jie He He Hu Xi Za Zhi 2001 24(5) 265-8
Page last reviewed: June 8, 2007 (archived document)
Page last updated: November 2, 2007
Content Source: National Office of Public Health Genomics