Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension

Abstract

Vascular endothelial growth factor (VEGF) is relevant for normal pregnancy, and abnormalities in VEGF functions are associated with hypertensive disorders of pregnancy. Because there are few studies on how VEGF genetic polymorphisms affect susceptibility to pre-eclampsia (PE), and no studies on how they affect susceptibility to gestational hypertension (GH), we compared VEGF genotype and haplotype distributions in normotensive and hypertensive pregnancies. Genotypes and haplotypes for VEGF polymorphisms (C-2578A, G-1154A and G-634C) were determined in 303 pregnant women (108 healthy pregnant, HP; 101 with GH and 94 with PE). When white and non-white pregnant women were considered together, no significant differences were found in the distributions of VEGF genotypes or haplotypes (P > 0.05) in the three groups. However, with only white subjects, significant differences were found in genotypes distributions for two (C-2578A and G-634C) VEGF polymorphisms (both P < 0.05) between the HP and the PE groups. Importantly, the haplotype including the variants C-2578, G-1154 and C-634, which is associated with higher VEGF gene expression, was less common in the PE group compared with the HP group (4% versus 16%; P = 0.0047). However, we found no significant differences in VEGF haplotypes distributions when the HP and GH groups were compared (P > 0.05). These findings suggest a protective effect for the 'C-2578, G-1154 and C-634' haplotype against the development of PE, but no major effects of VEGF gene variants on susceptibility to GH.

Vascular Endothelial Growth Factor Genetic Polymorphisms and Haplotypes in Women with Migraine

“…Although this difference could reflect interethnic heterogeneity in the distribution of VEGF polymorphisms (Muniz et al , 2009), we found that the H6 haplotype including the variants AGC was more frequent in patients with MA than in the control group when both analyses were carried out. This result is consistent with the suggestion that genetic determinants of complex diseases may be associated with disease conditions independently of ethnicity, as previously reported (Sandrim et al , 2006, 2007, 2008). The molecular mechanism explaining how these specific combinations (haplotypes) of VEGF gene variants are associated with migraine remains to be elucidated.…”

Vascular Endothelial Growth Factor Genetic Polymorphisms and Haplotypes in Women with Migraine

“…Although this difference could reflect interethnic heterogeneity in the distribution of VEGF polymorphisms (Muniz et al , 2009), we found that the H6 haplotype including the variants AGC was more frequent in patients with MA than in the control group when both analyses were carried out. This result is consistent with the suggestion that genetic determinants of complex diseases may be associated with disease conditions independently of ethnicity, as previously reported (Sandrim et al , 2006, 2007, 2008). The molecular mechanism explaining how these specific combinations (haplotypes) of VEGF gene variants are associated with migraine remains to be elucidated.…”

Polymorphisms and Haplotypes in Candidate Genes Related to Angiogenesis and Endothelial Dysfunction in Preeclampsia

“…The results from single locus analysis showed significant differences in the distribution of genotypes and alleles for the VEGF − 634G/C polymorphism when PE was compared to HP and for the MMP-9 − 1562C/T polymorphism when GH was compared to HP, respectively (all P < 0.05). These results are in agreement with our previous findings [2, 9]. However, we have observed a significant interaction between MMP-9 and VEGF genes associated with the PE group compared to HP [10].…”

MTHFR and F5 genetic variations have association with preeclampsia in Pakistani patients: a case control study

“…VEGF is expressed in the placenta and has a significant role in its development and maintenance. VEGFA variants have been widely studied and its association with preeclampsia has been found in several studies, including Chinese, Brazilian, Hungarian and Korean patients [42][43][44][45]. However, our study negates the association of VEGFA: c.-2055A > C and c.*237C > T variants with preeclampsia in Pakistani patients.…”

Vascular Endothelial Growth Factor Genetic Polymorphisms and Haplotypes in Women with Migraine

“…Although this difference could reflect interethnic heterogeneity in the distribution of VEGF polymorphisms (Muniz et al , 2009), we found that the H6 haplotype including the variants AGC was more frequent in patients with MA than in the control group when both analyses were carried out. This result is consistent with the suggestion that genetic determinants of complex diseases may be associated with disease conditions independently of ethnicity, as previously reported (Sandrim et al , 2006, 2007, 2008). The molecular mechanism explaining how these specific combinations (haplotypes) of VEGF gene variants are associated with migraine remains to be elucidated.…”

Polymorphisms and Haplotypes in Candidate Genes Related to Angiogenesis and Endothelial Dysfunction in Preeclampsia

“…The results from single locus analysis showed significant differences in the distribution of genotypes and alleles for the VEGF − 634G/C polymorphism when PE was compared to HP and for the MMP-9 − 1562C/T polymorphism when GH was compared to HP, respectively (all P < 0.05). These results are in agreement with our previous findings [2, 9]. However, we have observed a significant interaction between MMP-9 and VEGF genes associated with the PE group compared to HP [10].…”

MTHFR and F5 genetic variations have association with preeclampsia in Pakistani patients: a case control study

“…VEGF is expressed in the placenta and has a significant role in its development and maintenance. VEGFA variants have been widely studied and its association with preeclampsia has been found in several studies, including Chinese, Brazilian, Hungarian and Korean patients [42][43][44][45]. However, our study negates the association of VEGFA: c.-2055A > C and c.*237C > T variants with preeclampsia in Pakistani patients.…”

Vascular Endothelial Growth Factor Genetic Polymorphisms and Haplotypes in Women with Migraine

“…Although this difference could reflect interethnic heterogeneity in the distribution of VEGF polymorphisms (Muniz et al , 2009), we found that the H6 haplotype including the variants AGC was more frequent in patients with MA than in the control group when both analyses were carried out. This result is consistent with the suggestion that genetic determinants of complex diseases may be associated with disease conditions independently of ethnicity, as previously reported (Sandrim et al , 2006, 2007, 2008). The molecular mechanism explaining how these specific combinations (haplotypes) of VEGF gene variants are associated with migraine remains to be elucidated.…”

Polymorphisms and Haplotypes in Candidate Genes Related to Angiogenesis and Endothelial Dysfunction in Preeclampsia

“…The results from single locus analysis showed significant differences in the distribution of genotypes and alleles for the VEGF − 634G/C polymorphism when PE was compared to HP and for the MMP-9 − 1562C/T polymorphism when GH was compared to HP, respectively (all P < 0.05). These results are in agreement with our previous findings [2, 9]. However, we have observed a significant interaction between MMP-9 and VEGF genes associated with the PE group compared to HP [10].…”

MTHFR and F5 genetic variations have association with preeclampsia in Pakistani patients: a case control study

“…VEGF is expressed in the placenta and has a significant role in its development and maintenance. VEGFA variants have been widely studied and its association with preeclampsia has been found in several studies, including Chinese, Brazilian, Hungarian and Korean patients [42][43][44][45]. However, our study negates the association of VEGFA: c.-2055A > C and c.*237C > T variants with preeclampsia in Pakistani patients.…”