Thrombophilic risk factors are laterally associated with Apolipoprotein E gene polymorphisms in deep vein thrombosis patients: An Indian study

Abstract

Introduction

Deep vein thrombosis is a multifactorial disease with many acquired and genetic risk factors. Polymorphism in the APOE gene is an upcoming potential pathogenic factor whose role is unclear in deep vein thrombosis.

Methods

An equal number of deep vein thrombosis cases and controls (N = 100, each) were investigated for APOE gene polymorphisms along with known acquired and hereditable thrombophilic risk factors. APOE genotyping was done by polymerase chain reaction.

Results

The ε3/ε4 and ε2/ε3 APOE genotypes were commoner in deep vein thrombosis cases than controls but not statistically significant (ε3/ε4 → 18% versus 11%, OR = 1.776, CI = 0.792–3.984, p = 0.16; ε2/ε3 →10% versus 9%, OR = 1.123, CI = 0.436–2.895, p = 0.809). However, the following risk factors were found to be laterally associated with APOE genotypes in cases of deep vein thrombosis: pregnancy with ε2/ε3 genotype positivity (N = 29; p = 0.019), recurrent pregnancy loss with ε3/ε3 genotype (N = 29; p = 0.016), normal antithrombin levels with ε3/ε3 genotype (N = 62; p = 0.03) and non-O blood group with ε3/ε4 genotype (N = 100; p = 0.023).

Conclusion

APOE genotypes have shown only a modest association with deep vein thrombosis and were not statistically significant. A lateral association of these genotypes with thrombophilic risk factors was observed which may be investigated further for the possible pathogenetic mechanisms and their therapeutic implications.

Keywords

Apolipoprotein E deep vein thrombosis genetic polymorphism thrombophilia

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References

Heit

Phelps

Ward

et al . Familial segregation of venous thromboembolism. J Thromb Haemost 2004; 2: 731–736.

Morange

Trégouët

DA.

Current knowledge on the genetics of incident venous thrombosis.

J Thromb Haemost 2013; 11: 111–121.

Katrancioglu

Manduz

Ozen

et al . Association between ApoE4 allele and deep venous thrombosis: a pilot study. Clin Appl Thromb 2011; 17: 225–228.

Nagato

De Souza Pinhel

De Godoy

JMP

et al . Association of ApoE genetic polymorphisms with proximal deep venous thrombosis. J Thromb Thrombolysis 2012; 33: 116–119.

Zhu

Wang

et al . Apolipoprotein E polymorphism is associated with lower extremity deep venous thrombosis: color-flow Doppler ultrasound evaluation. Lipids Health Dis 2014; 13: 21.

Hedayati

Samadi

Apolipoprotein E Polymorphism in an Iranian Hypercholestrolemic Population. Iran Biomed J 2002; 6: 117–122.

Lusis

Heinzmann

Sparkes

et al . Regional mapping of human chromosome 19: organization of genes for plasma lipid transport (APOC1, -C2, and -E and LDLR) and the genes C3, PEPD, and GPI. Proc Natl Acad Sci USA 1986; 83: 3929–3933.

Mahfouz

RAR

Sabbagh

Zahed

et al . Apolipoprotein E gene polymorphism and allele frequencies in the Lebanese population. Mol Biol Rep 2006; 33: 145–149.

Mahley

RW.

Apolipoprotein E: cholesterol transport protein with expanding role in cell biology.

Science 1988; 240: 622–630.

10.

Eichner

Dunn

Perveen

et al . Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review. Am J Epidemiol 2002; 155: 487–495.

11.

Yip

McKee

Green

et al . APOE, vascular pathology, and the AD brain. Neurology 2005; 65: 259–265.

12.

Mrad

Fekih-Mrissa

Wathek

et al . Role of the apolipoprotein E polymorphisms in the development of retinal vein occlusion in a Tunisian population: a case-control study. Clin Appl Thromb 2016; 23: 645–651.

13.

Miyakis

Lockshin

Atsumi

et al . International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4: 295–306.

14.

Misra

Chowbey

Makkar

et al.

Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India 2009; 57: 163–170.

15.

Kearon

Ageno

Cannegieter

et al . Categorization of patients as having provoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost 2016; 14: 1480–1483.

16.

Ossendorf

Prellwitz

Rapid and easy apolipoprotein E genotyping using an improved PCR-RFLP technique. Qiagen News 2000; 1: 11–13.

17.

Thakur

Jeet

Pal

et al . Profile of risk factors for non-communicable diseases in Punjab, Northern India: results of a state-wide STEPS survey. PLoS One 2016; 11: e0157705.

18.

Heit

JA.

The epidemiology of venous thromboembolism in the community: implications for prevention and management.

J Thromb Thrombolysis 2006; 21: 23–29.

19.

D’Uva

Micco

P Di

Strina

et al . Recurrent pregnancy loss and thrombophilia. J Clin Med Res 2010; 2: 18–22.

20.

Holst

Jensen

Prescott

Risk factors for venous thromboembolism.

Circulation 2010; 121: 1896–1903.

21.

Cheng

Y-J

Liu

Z-H

Yao

F-J

et al . Current and former smoking and risk for venous thromboembolism: a systematic review and meta-analysis. PLoS Med 2013; 10: e1001515.

22.

Bruzelius

Bottai

Sabater-Lleal

et al . Predicting venous thrombosis in women using a combination of genetic markers and clinical risk factors. J Thromb Haemost 2015; 13: 219–227.

23.

Haan

HG De

Bezemer

Doggen

CJM

et al . Multiple SNP testing improves risk prediction of first venous thrombosis. Blood 2012; 120: 656–663.

24.

Ulrich

Konaniah

Herz

et al . Genetic variants of ApoE and ApoER2 differentially modulate endothelial function. Proc Natl Acad Sci USA 2014; 111: 13493–13498.

25.

Chen

et al . Apolipoprotein E (Apo E) gene polymorphisms and recurrent pregnancy loss: a meta-analysis. J Assist Reprod Genet 2014; 31: 139–148.

26.

Candás-Estébanez

Padró-Miquel

Ruiz-Iruela

et al . APOE variants E2, E3, and E4 can be miscalled by classical PCR-RFLP when the Christchurch variant is also present. J Clin Lab Anal 2017; 31: e22040.