VEGF and IL-4 gene variability and its association with the risk of coronary heart disease in north Indian population
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Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor that has been shown to play a significant role in neovascularization during inflammation in atherosclerotic plaques, formation of collateral vessels to an area of ischemic myocardium and neovascularization at the edges of a myocardial infarction during its repair. Interleukin-4 (IL-4) has important role in immune cell chemotaxis, formation of endothelial cell adhesion molecules and has numerous anti-inflammatory effects which prevent the complications of atherosclerosis, the primary cause of coronary heart disease (CHD). In this study, we have analyzed the effect of 1154 A/G polymorphism of VEGF and 70 bp VNTR polymorphism of intron 3 in IL-4 genes in coronary heart disease (CHD) patients (n = 300) and their age matched controls (n = 300). To analyze polymorphic alleles, ARMS-PCR and RFLP techniques were used. Multiple logistic regression analysis was carried out with statistical software. GG genotype was associated with a decreased risk of development of CHD (OR 0.22, 95% CI 0.12–0.38, P < 0.001). However, A allele showed an increased risk whereas G allele decreased the risk of CHD with diabetes mellitus, hypertension, chronic mental stress and positive familial history of myocardial infarction (MI)/CHD. GG genotype was found to have protective effect with alcohol intake (OR 0.34, 95% CI 0.14–0.82, P < 0.01) and central obesity (OR 0.15, 95% CI 0.04–0.56, P < 0.001). GG genotype of VEGF has also shown significant association with IL-4 (P2P2 and P1P2) genotypes.
KeywordsVEGF IL-4 Genetic polymorphism CHD Atherosclerosis Cytokine
This work was supported by a grant from Council of Scientific and Industrial Research, Ministry of Human Resource and Development, New Delhi, India. We thank Dr. Gurbir Singh and Dr. G. S. Kalra, Fortis Hospital, Mohali, India for their kind help and co-operation.
- 3.Clauss M, Gerlach M, Gerlach H, Brett J, Wamg F, Familletti PC, Pan YC, Olander JV, Connolly DT, Stern D (1990) Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 172:1535–1545CrossRefPubMedGoogle Scholar
- 8.Zhao Q, Egashira K, Inoue S, Usui M, Kitamoto S, Ni W, Ishibashi M, Hiasa Ki K, Ichiki T, Shibuya M, Takeshita A (2002) Vascular endothelial growth factor is necessary in the development of arteriosclerosis by recruiting/activating monocytes in a rat model of long-term inhibition of nitric oxide synthesis. Circulation 105:1110–1115CrossRefPubMedGoogle Scholar
- 24.Bijlsma FJ, Van K, Van H, Jonge E, Tilanus N, Gmelig-Meyling FH, de Weger RA (2002) Acute cardiac transplant rejection is associated with low frequencies of interleukin-4 producing helper T-lymphocytes rather than with interleukin-4 promoter or splice variants. Hum Immunol 63:317–323CrossRefPubMedGoogle Scholar
- 26.Nakayama EE, Meyer L, Iwamoto A, Persoz A, Nagai Y, Rouzioux C, Delfraissy JF, Debre P, McIlroy D, Theodorou I, Shioda T (2003) SEROCO Study Group Protective effect of interleukin-4589T polymorphism on human immunodeficiency virus type 1 disease progression: relationship with virus load. J Infect Dis 185:1183–1186CrossRefGoogle Scholar
- 35.Moulton KS, Vakili K, Zurakowski D, Soliman M, Butterfield C, Sylvin E, Lo KM, Gillies S, Javaherian K, Folkman J (2003) Inhibition of plaque neovascularization reduces marcrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci USA 100:4736–4741CrossRefPubMedGoogle Scholar
- 40.Mccarron SL, Edwards S, Evans PR, Gibbs R, Dearnaley DP, Dowe A, Southgate C, Easton DF, Feles RA, Howell WM (2002) Influence of cytokine gene polymorphisms on the development of prostate cancer. Cancer Res 12:3369–3372Google Scholar