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Polymorphism in the epidermal growth factor gene is associated with pre‐eclampsia and low birthweight
Author(s) -
Chenthuran Thurayratnam,
Galhenagey Gayani Harendra,
Jayasekara Rohan W.,
Dissanayake Vajira H. W.
Publication year - 2014
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/jog.12362
Subject(s) - single nucleotide polymorphism , odds ratio , snp , haplotype , medicine , preeclampsia , allele , birth weight , genetics , polymorphism (computer science) , population , genotype , biology , pregnancy , gene , environmental health
Aim We have previously reported that polymorphism in the epidermal growth factor ( EGF ) gene is associated with pre‐eclampsia and birthweight based on case–control association studies involving two single nucleotide polymorphisms ( SNP ). We extended that work to investigate other SNP in the EGF gene for their association with pre‐eclampsia and the weight of babies at birth. Material and Methods A population‐based DNA collection was genotyped to determine whether the selected SNP were polymorphic in the study population. In total, 175 women with pre‐eclampsia and 171 matched normotensive controls were genotyped for the polymorphic SNP using polymerase chain reaction/restriction fragment length polymorphism and MassARRAY S equenom iPLEX methodology. Results The rs3756261 A , rs4444903 G , rs2237051 G haplotype was associated with the highest increased risk of pre‐eclampsia (odds ratio: 3.70, 95% confidence interval: 1.38–9.94; P = 0.016). The rs3756261 A allele was the one that contributed to this high degree of significance. The same allele was present in the haplotype rs3756261 A , rs11568943 G , rs2237051 G , rs11569017 A , rs4698803 T (likelihood ratio statistic = 20.4671, d.f. = 3, P ‐value = 0.0001), which was associated with the lower birthweight. Conclusions In this study we found further evidence for the association of polymorphism in the EGF gene with pre‐eclampsia and the weight of babies at birth and identified rs3756261 A > G as the SNP that makes the most significant contribution to this association. Bioinformatic analysis showed that this effect may be mediated by caudal type homeohox‐2, a transcriptional repressor expressed in the trophoblast, for which a binding site is created at this polymorphic site when the rs3756261 A allele is present.