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Haplotypes of heparin-binding epidermal-growth-factor-like growth factor gene are associated with pre-eclampsia

Authors

  • Galhenagey Gayani Harendra,

    Corresponding author
    1. Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
      Mrs Galhenagey Gayani Harendra, Department of Zoology, Faculty of Science, University of Colombo, Colombo, Sri Lanka. Email: gayanihg@gmail.com
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  • Rohan W. Jayasekara,

    1. Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
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  • Vajira H. W. Dissanayake

    1. Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
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  • Present address: Galhenagey Gayani Harendra, Department of Zoology, Faculty of Science, University of Colombo, Colombo, Sri Lanka.

Mrs Galhenagey Gayani Harendra, Department of Zoology, Faculty of Science, University of Colombo, Colombo, Sri Lanka. Email: gayanihg@gmail.com

Abstract

Aim:  Heparin-binding epidermal-growth-factor-like growth factor (HBEGF) plays an important role in placentation, including impaired placentation, the primary defect seen in pre-eclampsia. We carried out a case–control disease-association study to examine the association of single nucleotide polymorphisms (SNP) in the HBEGF gene and haplotypes defined by them with pre-eclampsia in a Sinhalese population in Sri Lanka.

Materials and Methods:  A total of 175 women with pre-eclampsia and 171 matched normotensive controls were genotyped for six SNP selected in silico as having putative functional effects using mass array Sequenom iplex methodology and a newly designed polymerase chain reaction–restriction fragment length polymorphism assay.

Results:  The individual SNP were not associated with pre-eclampsia. The haplotypes defined by them, however, showed both predisposing (rs13385T,rs2074613G,rs2237076G,rs2074611C,rs4150196A,rs1862176A; odds ratio, 1.65; 95% confidence interval 1.04–2.60; P = 0.032) and protective (rs13385C,rs2074613G,rs2237076A,rs2074611C,rs4150196A,rs1862176A; odds ratio, 0.20; 95% confidence interval, 0.04–0.89; P = 0.034) effects.

Conclusions:  These results confirm that polymorphisms in the HGEGF gene are associated with pre-eclampsia. The haplotypes are likely to exert their effects through the numerous transcription regulation factors binding to the polymorphic sites, namely GATA-1, GATA-3, MZF-1 and AML-1a.

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