VEGF-A and VEGFR1 SNPs associate with preeclampsia in a Philippine population

Abstract

The vascular endothelial growth factor (VEGF) family is important for establishing normal pregnancy, and related single nucleotide polymorphisms (SNPs) are implicated in abnormal placentation and preeclampsia. We evaluated the association between preeclampsia and several VEGF SNPs among Filipinos, an ethnically distinct group with high prevalence of preeclampsia. The genotypes and allelic variants were determined in a case-control study (191 controls and 165 preeclampsia patients) through SNP analysis of VEGF-A (rs2010963, rs3025039) and VEGF-C (rs7664413) and their corresponding receptors VEGFR1 (rs722503, rs12584067, rs7335588) and VEGFR3 (rs307826) from venous blood DNA. VEGF-A rs3025039 C allele has been shown to associate with preeclampsia (odds ratio of 1.648 (1.03-2.62)), while the T allele bestowed an additive effect for the maintenance of normal, uncomplicated pregnancy and against the development of preeclampsia (odds ratio of 0.62 (0.39-0.98)). VEGFR1 rs722503 is associated with preeclampsia occurring at or after the age of 40 years. The results showed that genetic variability of VEGF-A and VEGFR1 are important in the etiology of preeclampsia among Filipinos.

Vascular endothelial growth factor +936C/T and -634G/C polymorphisms exhibited significantly different allelic distributions and no associations with the risk of preeclampsia, gestational hypertension or gestational diabetes mellitus in the Xinjiang Uygur Autonomous Region of China

“…Correlations between VEGF +936C/T and -634C/G gene polymorphisms and PE have been widely studied [17][18][19][20][21][22][23][24][25], but the conclusions of studies in different regions are inconsistent. Some studies had a small sample size (N≤100) [28,[40][41][42], which may have affected the accuracy of the results.…”

“…VEGF is thought to be involved in the pathogenesis of PE vascular injury. In reports of the relationship between the VEGF + 936C/T and − 634G/C polymorphisms and PE susceptibility [17][18][19][20][21][22][23][24][25][26][40][41][42], some reports indicated that the + 936C/T polymorphism was related to the risk of PE [17,[20][21][22], while other studies reported that the + 936C/T polymorphism was not associated with PE risk [18,19,23,24]. Similarly, regarding the relationship between the − 634G/C polymorphism and PE susceptibility, most of the results were negative [19,24,25], but there are also reports that this polymorphism is associated with severe PE [16].…”

“…Analysis of the possible factors affecting the results and speculation that certain clinical factors (such as the differences in the study area and population included in the study, the sample size, and the inclusion and exclusion criteria for the study group) may cause bias, resulting in false negative or false positive results. In addition, sPE and mPE have high clinical heterogeneity, and subgroup analysis is recommended, but only two of the above documents classi ed PE [16,21].…”

“…During embryonic development, VEGF expression can be initially detected in the giant cells of the trophoblast within the rst few days after implantation [8]. VEGF mRNA expression can be detected in almost all tissues in human foetuses (16)(17)(18)(19)(20)(21)(22) weeks) [2].…”

“…The VEGF + 936C/T and − 634C/G mutation sites have been shown to further affect the development of the disease by changing the transcription level and protein expression of VEGF [14][15][16]. There are many reports on the relationship between VEGF + 936C/T and − 634C/G and PE susceptibility [17][18][19][20][21][22][23][24][25]. However, the results are inconsistent across regions.…”