Vascular endothelial growth factor gene polymorphisms in North Indian patients with recurrent miscarriages

Abstract

The association of four common polymorphisms of vascular endothelial growth factors (VEGF) with recurrent miscarriages(RM) was evaluated in North Indian women for 200 patients with RM and 200 controls. The subjects were genotyped for the polymorphisms 2578C/A, 2549 18-bp I/D, 1154G/A and +936C/T. Association of VEGF genotypes, alleles and haplotypes with recurrent miscarriage were evaluated by Fisher’s exact test. 1154G/A and +936C/T modified the risk of RM. The 1154A allel and +936T allel significantly increased the risk of RM (OR = 1.485, P = 0.0210, 95% CI 1.072–2.057 and OR = 1.869, P = 0.0054, 95% CI 1.214–2.876 respectively). Risk was further increased when –1154A/A genotype and +936C/T genotype were considered (OR = 2.0, P = 0.0310,95% CI 1.068–3.747 and OR = 1.716, P = 0.0293, 95% CI 1.058–2.784 respectively). However, no association was found between 2578C/A or 2549 18-bp I/D and RM. Four haplotypes, AIAC, ADAC, CIAT and ADGT, were found to predispose to RM while the haplotypes CIAC, CDGT and ADGC were found to show protective effect. In conclusion, two common polymorphisms of the VEGF gene,1154G/A and +936C/T, increase the risk of RM in North Indian women. RM is also predisposed in the presence of haplotypes AIAC,ADAC, CIAT and ADGT.

Genetic variation in vascular endothelial growth factor gene and its association with recurrent spontaneous abortion

“…The lack of the association with RSA and +936C/T (rs3025039, 3´UTR region) in the current study was also reported in Bahraini (Brazilian, 27), Greek (28) and Korean (29) population studies while Aggarwal et al (19) studied North Indians and it was in disagreement with previous studies and our fi ndings. In the present study, we did not report +936 T allele frequency of both case and controls.…”

“…In the present study, we did not report +936 T allele frequency of both case and controls. Homozygosity for this allele is also rare (0.8-4 %) in different populations (19,28). The +936C/T SNP is located in 3´UTR region and was linked to altered VEGF expression in different studies (12, 30, 31).…”

“…The VEGF gene is located on human chromosome 6p21.3 and contains eight exons and seven introns forming several VEGF isoforms by alternative splicing in different cells (11). The several common VEGF polymorphism sites in promoter (-2578C/A, -1154G/A, -2549 18-bp I/D, -460C/T, -1498T/C, -1190G/A), the 5´UTR (-634G/C, -7T/ C ), the 3´UTR (+936C/T and +1612G/A) and intron (rs3025010) regions have been reported by various studies on RSA women of differrent ethnicities (12)(13)(14)(15)(16)(17)(18)(19).…”

Association of −2549 Insertion/Deletion Polymorphism of Vascular Endothelial Growth Factor with Breast Cancer in North Indian Patients

“…It has been reported that constructs containing the 18-bp deletion had a 1.95-fold increase in the transcriptional activity compared with those containing the insert (Yang et al, 2003). Contrary to previous reports of ID or DD genotypes being associated with systemic sclerosis in the European Caucasians (Allanore et al, 2007), HCC in the Chinese Han population (He et al, 2010), and in recurrent miscarriages in the North Indian population (Aggarwal et al, 2011), in the present study, frequencies of the II genotype and I allele were significantly higher in breast cancer patients than controls thus indicating a probable decreased transcriptional activity of VEGF in patients.…”

“…Several studies have analyzed the -2549 I/D polymorphism in the context of susceptibility to various diseases like Behcet's disease (BD) (Salvarani et al, 2004), asthma (Lachheb et al, 2008), HCC (He et al, 2010), recurrent miscarriages (Aggarwal et al, 2011), and end-stage renal disease (Prakash et al, 2012). Association of the DD genotype of the -2549 I/D polymorphism has been reported with diabetic retinopathy (Awata et al, 2002;Buraczynska et al, 2007), diabetic nephropathy (Yang et al, 2003), peripheral artery disease (Bleda et al, 2012), and end-stage renal disease (Prakash et al, 2012).…”