A polymorphic GT short tandem repeat affecting beta-ENaC mRNA expression is associated with low renin essential hypertension.
BACKGROUND
The epithelial sodium channel (ENaC) is a candidate gene associated with the development of essential hypertension. A potentially polymorphic repetitive region (GT dinucleotide short tandem repeat [STR]) was identified in intron 8 of beta-ENaC gene (SCNN1B). The aim of this study was to identify the prevalence and distribution of a polymorphic GT-STR in SCNN1B in Chilean essential hypertensive (EH) patients and to analyze the correlation between the different genotypes with plasma renin activity (PRA) and serum aldosterone (SA), and furthermore, to evaluate the beta-ENaC gene expression in vitro.


METHODS
We studied 133 patients with EH and 69 normotensive (NT). In both EH and NT subjects we measured PRA, SA, urine sodium, and genotyped them according to the GT-STR length using sequencing analysis. We detected 11, 13 and 14 GT alleles in EH and NT subjects. Both groups were classified according to genotype: 14/14, 14/13, 13/13, 13/11, and 11/11. Influence of the GT-STR on beta-ENaC minigene expression was evaluated by real-time polymerase chain reaction.


RESULTS
In EH, PRA decreased with the length of the STR region 11/13, 1.40 +/- 0.69; 13/13, 1.16 +/- 0.61; 13/14, 0.90 +/- 0.56; 14/14, 0.32 +/- 0.09 ng/mL/h; P < .01. Likewise, PRA in patients with EH with 14/14 or 14/13 genotypes were lower than EH with 13/13 or 13/11 genotypes (0.77 +/- 0.5 v 1.24 +/- 0.6 ng/mL/h; P < .01). Real-time polymerase chain reaction demonstrated an increased beta-ENaC expression in minigenes containing 14 GT-STR.


CONCLUSIONS
We have identified a polymorphic GT-STR in the beta-ENaC gene, which is present in the EH and NT Chilean population. Biochemical analysis showed a possible linkage between this polymorphic region and low renin hypertension. The in vitro assay suggests that GT-STR could regulate the beta-ENaC expression.
González
Alexis A
AA
Department of Endocrinology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Carvajal
Cristian A
CA
Riquelme
Erick
E
Krall
Paola M
PM
Munoz
Carlos R
CR
Mosso
Lorena M
LM
Kalergis
Alexis M
AM
Fardella
Carlos E
CE
D000328:Adult; D000450:Aldosterone / Q000097:blood*; D001794:Blood Pressure / Q000235:genetics; D016022:Case-Control Studies; D002677:Chile; D018900:Dinucleotide Repeats; D053503:Epithelial Sodium Channels / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D007438:Introns; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D012333:RNA, Messenger / Q000378:metabolism; D012083:Renin / Q000097:blood* / Q000172:deficiency; D012964:Sodium / Q000652:urine
D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; C507048:SCNN1B protein, human; D000450:Aldosterone; D012964:Sodium; D012083:Renin