The β-T594M polymorphism of the epithelial sodium channel (ENaC) has been associated with increased blood pressure in an English population of African ancestry (Baker et al., 1998) and Ghanaians in Kumasi (Dong et al., 2002) whereas no similar association was found in a South African population (Nkeh et al., 2003) although the β-R563Q mutation of ENaC has been associated with hypertension in South African blacks of mixed ancestry (Dhanjal et al., 2006). This study was designed to determine the presence or otherwise of ENaC polymorphisms among Nigerians as a prelude to establishing the relationship to hypertension among this population. One hundred healthy volunteers – 47 normotensive (NT) ) (age 41.23±1.40y) and 53 age-matched hypertensive (HT) (age 44.42±1.28y) – were recruited for this study after informed consent was obtained from them. Ethical approval (CM/COM/8/Vol. XXI) was granted by the College of Medicine University of Lagos Research Grants and Experimentation Ethics Committee. After baseline measurements, whole blood samples were obtained from the cubital vein in potassium ethylenediaminetetraacetic acid (K-EDTA) anticoagulated sample bottles and stored on a filter paper which was then stored in the refrigerator until analysis. DNA was then isolated followed by amplification by polymerase chain reaction (PCR). The amplicons were then sequenced for β-ENaC polymorphisms. Values are compared by Z-test. Five (5.0%) of the subjects had the β-T594M polymorphism, three of these were HT (3/53) while the remaining two were NT (2/47) (p = 0.75). Another polymorphism, β-T577t was observed in three HT (3/53) and one NT (1/47) (p = 0.37). Four previously unreported mutations were also recorded: β-E632V and β-E636V respectively among two (2/53) HT subjects and β-D638Y in another HT subject (1/53) while β-L628Q was recorded in one NT (1/47) subject. The results are interesting in that despite the small sample size, β-ENaC polymorphisms were recorded in a significant proportion (13/100) of the subjects. All the subjects with the β-T594M mutation in this study were heterozygous for the mutation which was present on the reverse strand. It is interesting that two of the subjects were normotensive. The β-T577t polymorphism is not likely to be of any consequence with regard to the development of hypertension since this is a silent mutation while all the new mutations, β-E632V, β-E636V, β-D638Y and β-L638Q, are non-synonymous changes and quite likely will have an effect on blood pressure. That these polymorphisms are however not limited to hypertensive subjects alone might be a pointer to the fact that salt sensitivity is a spectrum.
Epithelia and Smooth Muscle Interactions in Health and Disease (Dublin) (2013) Proc Physiol Soc 30, C13 and PC13
Oral Communications: (New) Polymorphisms of β-ENaC among Nigerians – a pilot study
S. Elias1, O. A. Sofola2, S. I. Jaja2
1. Physiology, Lagos State University College of Medicine, Lagos, Nigeria. 2. Physiology, College of Medicine of The University of Lagos, Lagos, Nigeria.
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Where applicable, experiments conform with Society ethical requirements.