Association of hypertension with T594M mutation in β subunit of epithelial sodium channels in black people resident in London

E. H. Baker, Yanbin Dong, G. A. Sagnella, M. Rothwell, A. K. Onipinla, N. D. Markandu, F. P. Cappuccio, D. G. Cook, A. Persu, P. Corvol, X. Jeunemaitre, N. D. Carter, G. A. MacGregor

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Abstract

Background. Liddle's syndrome is a rare inherited form of hypertension in which mutations of the epithelial sodium channel result in increased renal sodium reabsorption. Essential hypertension in black patients also shows clinical features of sodium retention so we screened black people for the T594M mutation, the most commonly identified sodium-channel mutation. Methods. In a case-control study, 206 hypertensive (mean age 48.0 [SD 11.8] years, men:women 80:126) and 142 normotensive [48.7 [7.4] years; 61:81) black people who lived in London, UK, were screened for T594M. Part of the last exon of the epithelial sodium-channel β subunit from genomic DNA was amplified by PCR. The T594M variant was detected by single-strand conformational polymorphism analysis of PCR products and confirmed by DNA sequencing. Findings. 17 (8.3%) of 206 hypertensive participants compared with three (2.1%) of 142 normotensive participants possessed the T594M (odds ratio [OR] = 4.17 [95% CI 1.12-18.25], p = 0.029). A high proportion of participants with the T594M variant were women (15 of 17 hypertensive participants and all three normotensive participants), whereas women comprised a lower proportion of the individuals screened (61.2% hypertensive, 57.7% normotensive). However, the association between the T594M variant and hypertension persisted after adjustment for sex and body-mass index (Mantel-Haenszel OR = 5.52 [1.40-30.61], p = 0.012). Plasma renin activity was significantly lower in 13 hypertensive participants with the T594M variant (median = 0.19 ng mL-1 h-1) than in 39 untreated hypertensive individuals without the variant (median = 0.45 ng mL-1 h-1, p = 0.009). Interpretation. Among black London people the T594M sodium-channel β subunit mutation occurs more frequently in people with hypertension than those without. The T594M variant may increase sodium-channel activity and could raise blood pressure in affected people by increasing renal tubular sodium reabsorption. These findings suggest that the T594M mutation could be the most common secondary cause of essential hypertension in black people identified to date.

Original languageEnglish (US)
Pages (from-to)1388-1392
Number of pages5
JournalLancet
Volume351
Issue number9113
DOIs
StatePublished - May 9 1998
Externally publishedYes

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Epithelial Sodium Channels
Sodium Channels
Hypertension
Mutation
Sodium
Liddle Syndrome
Odds Ratio
Polymerase Chain Reaction
DNA Sequence Analysis
Renin
Case-Control Studies
Exons
Body Mass Index
Blood Pressure
Kidney
DNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Baker, E. H., Dong, Y., Sagnella, G. A., Rothwell, M., Onipinla, A. K., Markandu, N. D., ... MacGregor, G. A. (1998). Association of hypertension with T594M mutation in β subunit of epithelial sodium channels in black people resident in London. Lancet, 351(9113), 1388-1392. https://doi.org/10.1016/S0140-6736(97)07306-6

Association of hypertension with T594M mutation in β subunit of epithelial sodium channels in black people resident in London. / Baker, E. H.; Dong, Yanbin; Sagnella, G. A.; Rothwell, M.; Onipinla, A. K.; Markandu, N. D.; Cappuccio, F. P.; Cook, D. G.; Persu, A.; Corvol, P.; Jeunemaitre, X.; Carter, N. D.; MacGregor, G. A.

In: Lancet, Vol. 351, No. 9113, 09.05.1998, p. 1388-1392.

Research output: Contribution to journalArticle

Baker, EH, Dong, Y, Sagnella, GA, Rothwell, M, Onipinla, AK, Markandu, ND, Cappuccio, FP, Cook, DG, Persu, A, Corvol, P, Jeunemaitre, X, Carter, ND & MacGregor, GA 1998, 'Association of hypertension with T594M mutation in β subunit of epithelial sodium channels in black people resident in London', Lancet, vol. 351, no. 9113, pp. 1388-1392. https://doi.org/10.1016/S0140-6736(97)07306-6
Baker, E. H. ; Dong, Yanbin ; Sagnella, G. A. ; Rothwell, M. ; Onipinla, A. K. ; Markandu, N. D. ; Cappuccio, F. P. ; Cook, D. G. ; Persu, A. ; Corvol, P. ; Jeunemaitre, X. ; Carter, N. D. ; MacGregor, G. A. / Association of hypertension with T594M mutation in β subunit of epithelial sodium channels in black people resident in London. In: Lancet. 1998 ; Vol. 351, No. 9113. pp. 1388-1392.
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abstract = "Background. Liddle's syndrome is a rare inherited form of hypertension in which mutations of the epithelial sodium channel result in increased renal sodium reabsorption. Essential hypertension in black patients also shows clinical features of sodium retention so we screened black people for the T594M mutation, the most commonly identified sodium-channel mutation. Methods. In a case-control study, 206 hypertensive (mean age 48.0 [SD 11.8] years, men:women 80:126) and 142 normotensive [48.7 [7.4] years; 61:81) black people who lived in London, UK, were screened for T594M. Part of the last exon of the epithelial sodium-channel β subunit from genomic DNA was amplified by PCR. The T594M variant was detected by single-strand conformational polymorphism analysis of PCR products and confirmed by DNA sequencing. Findings. 17 (8.3{\%}) of 206 hypertensive participants compared with three (2.1{\%}) of 142 normotensive participants possessed the T594M (odds ratio [OR] = 4.17 [95{\%} CI 1.12-18.25], p = 0.029). A high proportion of participants with the T594M variant were women (15 of 17 hypertensive participants and all three normotensive participants), whereas women comprised a lower proportion of the individuals screened (61.2{\%} hypertensive, 57.7{\%} normotensive). However, the association between the T594M variant and hypertension persisted after adjustment for sex and body-mass index (Mantel-Haenszel OR = 5.52 [1.40-30.61], p = 0.012). Plasma renin activity was significantly lower in 13 hypertensive participants with the T594M variant (median = 0.19 ng mL-1 h-1) than in 39 untreated hypertensive individuals without the variant (median = 0.45 ng mL-1 h-1, p = 0.009). Interpretation. Among black London people the T594M sodium-channel β subunit mutation occurs more frequently in people with hypertension than those without. The T594M variant may increase sodium-channel activity and could raise blood pressure in affected people by increasing renal tubular sodium reabsorption. These findings suggest that the T594M mutation could be the most common secondary cause of essential hypertension in black people identified to date.",
author = "Baker, {E. H.} and Yanbin Dong and Sagnella, {G. A.} and M. Rothwell and Onipinla, {A. K.} and Markandu, {N. D.} and Cappuccio, {F. P.} and Cook, {D. G.} and A. Persu and P. Corvol and X. Jeunemaitre and Carter, {N. D.} and MacGregor, {G. A.}",
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T1 - Association of hypertension with T594M mutation in β subunit of epithelial sodium channels in black people resident in London

AU - Baker, E. H.

AU - Dong, Yanbin

AU - Sagnella, G. A.

AU - Rothwell, M.

AU - Onipinla, A. K.

AU - Markandu, N. D.

AU - Cappuccio, F. P.

AU - Cook, D. G.

AU - Persu, A.

AU - Corvol, P.

AU - Jeunemaitre, X.

AU - Carter, N. D.

AU - MacGregor, G. A.

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N2 - Background. Liddle's syndrome is a rare inherited form of hypertension in which mutations of the epithelial sodium channel result in increased renal sodium reabsorption. Essential hypertension in black patients also shows clinical features of sodium retention so we screened black people for the T594M mutation, the most commonly identified sodium-channel mutation. Methods. In a case-control study, 206 hypertensive (mean age 48.0 [SD 11.8] years, men:women 80:126) and 142 normotensive [48.7 [7.4] years; 61:81) black people who lived in London, UK, were screened for T594M. Part of the last exon of the epithelial sodium-channel β subunit from genomic DNA was amplified by PCR. The T594M variant was detected by single-strand conformational polymorphism analysis of PCR products and confirmed by DNA sequencing. Findings. 17 (8.3%) of 206 hypertensive participants compared with three (2.1%) of 142 normotensive participants possessed the T594M (odds ratio [OR] = 4.17 [95% CI 1.12-18.25], p = 0.029). A high proportion of participants with the T594M variant were women (15 of 17 hypertensive participants and all three normotensive participants), whereas women comprised a lower proportion of the individuals screened (61.2% hypertensive, 57.7% normotensive). However, the association between the T594M variant and hypertension persisted after adjustment for sex and body-mass index (Mantel-Haenszel OR = 5.52 [1.40-30.61], p = 0.012). Plasma renin activity was significantly lower in 13 hypertensive participants with the T594M variant (median = 0.19 ng mL-1 h-1) than in 39 untreated hypertensive individuals without the variant (median = 0.45 ng mL-1 h-1, p = 0.009). Interpretation. Among black London people the T594M sodium-channel β subunit mutation occurs more frequently in people with hypertension than those without. The T594M variant may increase sodium-channel activity and could raise blood pressure in affected people by increasing renal tubular sodium reabsorption. These findings suggest that the T594M mutation could be the most common secondary cause of essential hypertension in black people identified to date.

AB - Background. Liddle's syndrome is a rare inherited form of hypertension in which mutations of the epithelial sodium channel result in increased renal sodium reabsorption. Essential hypertension in black patients also shows clinical features of sodium retention so we screened black people for the T594M mutation, the most commonly identified sodium-channel mutation. Methods. In a case-control study, 206 hypertensive (mean age 48.0 [SD 11.8] years, men:women 80:126) and 142 normotensive [48.7 [7.4] years; 61:81) black people who lived in London, UK, were screened for T594M. Part of the last exon of the epithelial sodium-channel β subunit from genomic DNA was amplified by PCR. The T594M variant was detected by single-strand conformational polymorphism analysis of PCR products and confirmed by DNA sequencing. Findings. 17 (8.3%) of 206 hypertensive participants compared with three (2.1%) of 142 normotensive participants possessed the T594M (odds ratio [OR] = 4.17 [95% CI 1.12-18.25], p = 0.029). A high proportion of participants with the T594M variant were women (15 of 17 hypertensive participants and all three normotensive participants), whereas women comprised a lower proportion of the individuals screened (61.2% hypertensive, 57.7% normotensive). However, the association between the T594M variant and hypertension persisted after adjustment for sex and body-mass index (Mantel-Haenszel OR = 5.52 [1.40-30.61], p = 0.012). Plasma renin activity was significantly lower in 13 hypertensive participants with the T594M variant (median = 0.19 ng mL-1 h-1) than in 39 untreated hypertensive individuals without the variant (median = 0.45 ng mL-1 h-1, p = 0.009). Interpretation. Among black London people the T594M sodium-channel β subunit mutation occurs more frequently in people with hypertension than those without. The T594M variant may increase sodium-channel activity and could raise blood pressure in affected people by increasing renal tubular sodium reabsorption. These findings suggest that the T594M mutation could be the most common secondary cause of essential hypertension in black people identified to date.

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