HFE Gene Polymorphism and Iron Status in Preeclampsia

Abstract

BACKGROUND Over the past decade, with the development of the genome-wide association studies, a dramatic increase of identification of many biological candidate gene mutations and polymorphisms have been examined in association with preeclampsia in its molecular etiopathogenesis. Preeclampsia is one of the leading causes of morbidity and mortality in pregnant women, if not attended. This study attempts to determine the association if any between C282Y allele of HFE gene with preeclampsia, and evaluate the serum iron status in women with preeclampsia and third trimester healthy pregnant women, as this polymorphism is closely associated with haemochromatosis, a hereditary disorder in which serum iron is elevated, which is also seen in pre-eclampsia. METHODS This is a hospital-based case-control study. Study was performed on one hundred pregnant women of 28 to 34 weeks gestation. Fifty preeclamptic women and fifty healthy pregnant women were taken as cases and controls respectively. Whole blood was taken for the extraction of DNA, followed by PCR and gel electrophoresis for the HFE gene polymorphism study and complete blood count analysis. Serum was used for iron, Total Iron Binding Capacity (TIBC) and ferritin estimations. Statistical significance was determined by calculating odds ratio for HFE gene polymorphism study and students t-test for other parameters. p-value of less than 0.05 was considered statistically significant. RESULTS There is no significant association between preeclampsia and HFE gene and C282Y allele polymorphism. 92% of the cases and 98% of the controls do not show mutation in the C282Y allele. Odds ratio for wild type is 1.065 and that of heterozygote is 4.261. 95% confidence interval is large (0.021-54.76), indicating a low level of precision in wild type. Z value for wild type is 0.031 and that of heterozygote is 1.275, p-value for both is not significant. Serum iron, ferritin and %age of transferrin saturation were significantly higher (p= 0.001) in preeclamptic women, in comparison with the control group. Unsaturated Iron Binding Capacity (UIBC) and TIBC were significantly lower (p=0.001) in preeclamptic group. CONCLUSIONS There are increased iron indices in preeclampsia when compared to the controls. Haemoglobin concentration and Haematocrit are raised in preeclampsia. There is no association of C282Y mutation of HFE gene with preeclampsia. Therefore, C282Y allele cannot be used as a molecular marker for preeclampsia.