Computational analysis of candidate disease genes and variants for salt-sensitive hypertension in indigenous Southern Africans.
Multiple factors underlie susceptibility to essential hypertension, including a significant genetic and ethnic component, and environmental effects. Blood pressure response of hypertensive individuals to salt is heterogeneous, but salt sensitivity appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select and prioritize candidate aetiological genes for salt-sensitive hypertension. Additionally, we have compared allele frequencies and copy number variation for single nucleotide polymorphisms in candidate genes between indigenous Southern African and Caucasian populations, with the aim of identifying candidate genes with significant variability between the population groups: identifying genetic variability between population groups can exploit ethnic differences in disease prevalence to aid with prioritisation of good candidate genes. Our top-ranking candidate genes include parathyroid hormone precursor (PTH) and type-1 angiotensin II receptor (AGTR1). We propose that the candidate genes identified in this study warrant further investigation as potential aetiological genes for salt-sensitive hypertension.
Tiffin
Nicki
N
Division of Nephrology and Hypertension, University of Cape Town/Groote Schuur Hospital, Cape Town, South Africa. nickitiffin@imaginet.co.za
Meintjes
Ayton
A
Ramesar
Rajkumar
R
Bajic
Vladimir B
VB
Rayner
Brian
B
D000353:Africa, Southern / Q000208:ethnology; D044383:Black People / Q000235:genetics; D019295:Computational Biology; D018628:Gene Dosage; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D006973:Hypertension / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012965:Sodium Chloride / Q000378:metabolism*; D044465:White People / Q000235:genetics
D012965:Sodium Chloride