Adrenomedullin gene polymorphisms (rs4399321A/G and rs4910118C/T) in pregnancy related disorder: Preeclampsia

Author(s): Goske Deepthi, Komaravalli Prasanna Latha, Vital Usharani, Prof. P. Fazul Rahman, Parveen Jahan

Preeclampsia (PE), a pregnancy specific vascular disorder which is characterized by hypertension and proteinuria is a leading cause of maternal, fetal/neonatal morbidity and mortality affecting 5-14% of pregnancies. PE is a multifactorial disorder associated with poor placentation, placental hypoxia, poor angiogenesis and excessive maternal inflammation. Adrenomedullin (ADM) is a multifunctional peptide, plays an important role in the establishment and maintenance of healthy pregnancy, prevents an immune attack at peri-implantation period, vasodilation and promotes angiogenesis. In the present study, we enrolled a total of 600 subjects which includes 300 PE patients and 300 healthy pregnant women from South India to analyse two functional polymorphisms (rs4399321A/G and rs4910118C/T) of ADM gene. The genotype frequencies of these two polymorphisms differed significantly between the PE and control groups (p=0.02 and p=0.03). Individuals carrying the AA genotype of rs4399321A/G were slightly higher in controls (40%) compared to patients (28%) and revealed an OR value of (0.69, CI 0.49-0.98; p=0.05) suggests the protective role. Predominant frequency of CC genotype of rs4910118C/T was observed in patients (OR- 1.43; CI 1.02–2.01, p=0.04) and CT genotype in controls (OR-0.69; CI 0.49–0.97, p=0.04) indicating predisposing and protective role of these genotypes. Haplotype analysis revealed a substantial association of A-T block towards preeclampsia with an OR value of 0.40 (CI 0.21-0.75, p=0.004). Further analysis on linkage disequilibrium showed a significant value (D’=1.0 and r2=0.12, p<0.05) between these two polymorphisms.

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