Four polymorphisms of VEGF (+405C>G, -460T>C, -2578C>A, and -1154G>A) in susceptibility to psoriasis: a meta-analysis

Abstract

The contribution of genetic polymorphisms in the vascular endothelial growth factor (VEGF) gene to psoriasis risk is a controversial topic. The aim of this meta-analysis was to investigate large-scale evidence to determine the degree to which four common VEGF polymorphisms (+405C>G [dbSNP: rs2010963], -460T>C [dbSNP: rs833061], -2578C>A [dbSNP: rs699947], and -1154G>A [dbSNP: rs1570360]) are associated with susceptibility to psoriasis. A literature search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Database was conducted to identify all eligible studies published before September 15, 2013. The principal outcome measure for evaluating the strength of the association was crude odds ratios (ORs) along with their corresponding 95% confidence intervals (95% CIs). Two thousand five hundred thirty-one patients and 2670 controls from nine case-control studies detailing a possible association between the VEGF genotypes and psoriasis risk were selected. Our meta-analysis provides evidence that two independent alleles +405G and -460C may be a protective factor for psoriasis in Asians, whereas the -1154A allele had a slight but statistically significant preventive effect on the development of psoriasis in Caucasians. The -2578C>A polymorphism, however, did not correlate with any significant difference between patients and healthy controls, even when the groups were stratified by ethnicity. Results from the meta-analysis do support the hypothesis that single-nucleotide polymorphism markers at +405C>G, -460C>T, and -1154G>A of the VEGF gene may serve as biological markers of psoriasis. Future studies should investigate interactions among multiple genotypes and environmental exposures to identify the role of proangiogenic markers in psoriasis and to delineate the underlying mechanisms of psoriasis.

FIG. 1.

Flow diagram of the selection of studies and specific reasons for exclusion from the present meta-analysis.

FIG. 2.

Forest plot of ORs for the association of VEGF +405C>G polymorphism with psoriasis risk in subgroup analysis based on ethnicity (A) dominant model; (B) homozygous model. CI, confidence interval; ORs, odds ratios.

FIG. 3.

Forest plot of ORs for the association of VEGF −460C>T polymorphism with psoriasis risk in subgroup analysis based on ethnicity (A) allele model; (B) homozygous model.

FIG. 4.

Sensitivity analysis of the summary odds ratio coefficients of VEGF gene polymorphisms are illustrated under the dominant model. Results were computed by omitting each study in turn. The two ends of the dotted lines represent the 95% CI (A) +405C>G; (B) −460C>T; (C) −2578C>A; (D) −1154G>A.

FIG. 5.

Begg's funnel plot of publication bias in selection of studies on VEGF gene polymorphisms are illustrated (A) +405C>G; (B) −460C>T; (C) −2578C>A; (D) −1154G>A. Each point represents a separate study by the indicated association. Log(OR), natural logarithm of OR. Horizontal line, mean magnitude of the effect.