Contribution of VEGF polymorphisms to variation in VEGF serum levels in a healthy population

Al-Habboubi, Heba H.; Sater, Mai S.; Almawi, A.W.; Al-Khateeb, Ghada; Almawi, Wassim Y.

doi:10.1684/ecn.2011.0289

Cited by 64 publications

(63 citation statements)

References 21 publications

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“…Prior studies involving these allelic variants support this conclusion, since the VEGF-A SNP investigated (rs3025039) has been repeatedly linked to decreased plasma levels of VEGF and reduced breast cancer risk, [31–33] while the IGFR1 SNP investigated (rs2016347) has not only been previously associated with breast density but also found to be an independent prognostic marker for breast cancer recurrence [34, 35]). While these various sources of evidence make it unlikely that these two SNPs found to modulate the significant association between PIH and %FGV were simply false positive discoveries, these novel observations require additional validation in larger population-based studies given the strong inheritance pattern underlying breast density.…”

Section: Discussionmentioning

confidence: 92%

First pregnancy events and future breast density: modification by age at first pregnancy and specific VEGF and IGF1R gene variants

Prebil

Ereman

Powell

et al. 2014

Cancer Causes Control

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Purpose Pregnancy characteristics have been associated with breast cancer risk, but information is limited on their relationship with breast density. Our objective was to examine the relationship between first pregnancy characteristics and later life breast density, and whether the association is modified by genotype.Methods The Marin Women’s Study was initiated to examine breast cancer in a high-incidence mammography population (Marin County, CA). Reproductive characteristics and pregnancy information including pregnancy-induced hypertension (PIH) were self-reported at the time of mammography. Forty-seven candidate single nucleotide polymorphisms were obtained from saliva samples; seven were assessed in relation to PIH and percent fibroglandular volume (%FGV). Breast density assessed as %FGV was measured on full-field digital mammograms by the San Francisco Mammography Registry.ResultsA multivariable regression model including 2,440 parous women showed that PIH during first pregnancy was associated with a statistically significant decrease in %FGV (b = −0.31, 95 % CI −0.52, −0.11), while each month of breast-feeding after first birth was associated with a statistically significant increase in %FGV (b = 0.01, 95 % CI 0.003, 0.02). PIH and breast-feeding associations with %FGV were modified by age at first birth. In a subsample of 1,240 women, there was evidence of modification in the association between PIH and %FGV by specific vascular endothelial growth factor (VEGF) (rs3025039) and insulin growth factor receptor-1 (IGFR1) (rs2016347) gene variants.ConclusionThese findings suggest that first pregnancy characteristics may exert an influence on extent of breast density later in life and that this influence may vary depending on inherited IGFR1 and VEGF genotypes.Electronic supplementary materialThe online version of this article (doi:10.1007/s10552-014-0386-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 92%

First pregnancy events and future breast density: modification by age at first pregnancy and specific VEGF and IGF1R gene variants

Prebil

Ereman

Powell

et al. 2014

Cancer Causes Control

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“…MAF of rs699947, rs25648, and rs833070 established for Tunisians was comparable to Bahraini Arabs [21] and Europeans [18,22] but was higher than rates established for Asians [22,23], Sub-Saharan Africans, and African Americans [24] (Table 5). On the other hand, MAF of rs833061, rs2010963, and rs3025039 does not appear to be racially influenced, and the MAF of rs833068 in Tunisians was comparable to the frequencies seen in Bahraini Arabs [21] and Caucasians [18,22], but lower than the rates reported for Asians or Africans [24] (Table 5). Collectively, this underscores the influence of racial background on the genotype distribution of a given SNP, and hence its disease association.…”

Section: Discussionmentioning

confidence: 73%

“…MAF of VEGF SNPs established for Tunisians were generally comparable to those of Caucasians [18,21]. MAF of rs699947, rs25648, and rs833070 established for Tunisians was comparable to Bahraini Arabs [21] and Europeans [18,22] but was higher than rates established for Asians [22,23], Sub-Saharan Africans, and African Americans [24] (Table 5).…”

Section: Discussionmentioning

confidence: 79%

“…We included SNPs in the 5 0 -UTR (rs699947, rs1570360, rs2010963, and rs833061) and 3 0 -UTR (rs3025039) VEGF regions which contain regulatory elements that contributes to the high variability in VEGF secretion, as well as in intron 2 (rs833068, rs833070) regions of VEGF gene. While 5 0 -UTR and 3 0 -UTR SNPs act by altering VEGF secretion [17,21], expanding evidence support a role for the intronic SNPs in modulating VEGF secretion and functional association. This was based on the finding that some VEGFA introns contain transcription factor binding sites, which in turn may influence the levels of VEGF production, and/or modulate mRNA splicing and processing [12].…”

Section: Discussionmentioning

confidence: 99%

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Relationship of common vascular endothelial growth factor polymorphisms and haplotypes with the risk of cervical cancer in Tunisians

et al. 2015

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“…VEGF is encoded by VEGFA gene, which is located on chromosome 6 (6p21.3), and comprises eight exons separated by seven introns [14]. Several single nucleotide polymorphisms (SNPs) were identified within the VEGFA gene, of which some were functional, directly affecting VEGF secretion [15–17]. These include -2578C/A and -1154G/A (promoter), -583T/C (intron 6), -634G/C and +963C/T (5’-untranslated region), which were linked with decreased VEGF production [15, 17, 18], whereas -460T/C and +534C/T were associated with higher VEGF secretion [16, 18].…”

Section: Introductionmentioning

confidence: 99%

Analysis of VEGFA Variants and Changes in VEGF Levels Underscores the Contribution of VEGF to Polycystic Ovary Syndrome

et al. 2016

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BackgroundVascular endothelial growth factor (VEGF) contributes to the pathogenesis of polycystic ovary syndrome (PCOS), and genetic variations in VEGFA gene were suggested to contribute to VEGF secretion and PCOS.AimTo evaluate the association of altered VEGF levels, stemming from the presence of specific VEGFA variants, with altered risk of PCOS.Subjects and MethodsRetrospective case-control study, performed between 2012–2015. Study subjects comprised 382 women with PCOS, and 393 control subjects. ELISA measured VEGF levels; genotyping of VEGFA variants was done by allelic exclusion.ResultsAmong the 12 tested VEGFA SNPs, minor allele frequency of only rs3025020 was significantly higher in PCOS cases than control women. Increased and reduced PCOS risk was seen with rs3025020 and rs2010963 genotypes, respectively. Increases and reduction in VEGF levels were associated with rs3025020 and rs2010963, respectively. Increased fasting insulin and HOMA-IR, and bioactive testosterone were linked with rs3025020, while carriage of rs2010963 was linked with reduction in fasting insulin, and free and bioactive testosterone. Of the 12 VEGFA variants, 9 were in LD, thus allowing construction of 9-locus haplotypes. Increased frequency of CAACAGCGA haplotype was seen in PCOS cases, after controlling for BMI, free and bioactive testosterone, SHBG, free insulin and HOMA-IR.ConclusionThis study confirms the contribution of altered VEGF secretion, resulting from genetic variation in VEGFA gene into the pathogenesis of PCOS. This supports a role for VEGF as PCOS candidate locus.

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Contribution of VEGF polymorphisms to variation in VEGF serum levels in a healthy population

Cited by 64 publications

References 21 publications

First pregnancy events and future breast density: modification by age at first pregnancy and specific VEGF and IGF1R gene variants

First pregnancy events and future breast density: modification by age at first pregnancy and specific VEGF and IGF1R gene variants

Relationship of common vascular endothelial growth factor polymorphisms and haplotypes with the risk of cervical cancer in Tunisians

Analysis of VEGFA Variants and Changes in VEGF Levels Underscores the Contribution of VEGF to Polycystic Ovary Syndrome

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