The evaluation of VEGF and HIF-1α gene polymorphisms and multiple sclerosis susceptibility

Multiple sclerosis (MS) is an autoimmune disease that leads to myelin sheath destruction. Hypoxia-inducible factor 1 (HIF-1) has several roles in cells, such as inducing inflammation and angiogenesis. Recently, several lines of evidence have indicated the role of the hypoxia response and the HIF-1 signaling pathway in an autoimmune disease such as MS. The present study aimed to evaluate the effects of HIF-1α gene polymorphisms and vascular endothelial growth factor (VEGF) (as a major target gene of HIF-1α) gene polymorphism on MS susceptibility.

In total, 150 MS patients and 150 healthy age- and gender-matched people as a control group participated in the present study. The polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping.

The results obtained showed that the CC genotype of the VEGF rs699947 polymorphism was significantly higher in the case group than in the control group (p = 0.004). Also, we showed a significant relationship between the VEGF rs699947 polymorphism and MS in a dominant inheritance model (p = 0.005). Regarding the VEGF rs699947 polymorphism allelic distribution, the C allele frequency was significantly higher in the control group than in the case group (71.3% versus 61%, respectively, p = 0.009) and decreased the MS susceptibility by 1.6-fold (odds ratio = 1.6, 95% confidence interval = 1.2-2.2). There was no significant difference between the two groups with respect to HIF-1α rs11549465 genotypic distribution. The HIF-1α C111A polymorphism was non-polymorphic in our study population, except in the case group where nine subjects carried the CA genotype.

We show a significant association between VEGF rs60047 polymorphism and MS susceptibility. However, our results do not show a significant association between MS and HIF-1α polymorphisms.