ASSOCIATION OF HYPERTENSION WITH T594M MUTATION IN BETA-SUBUNIT OF EPITHELIAL SODIUM-CHANNELS IN BLACK-PEOPLE RESIDENT IN LONDON

Background. Liddle's syndrome is a rare inherited form of hypertension in which mutations of the epithelial sodium channel result in increas ed 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-ch annel mutation. Methods. In a case-control study, 206 hypertensive (me an age 48.0 [SD 11.8] years, men:women 80:126) and 142 normotensive (4 8.7 [7.4] years; 61:81) black people who lived in London, UK, were scr eened for T594M. Part of the last exon of the epithelial sodium-channe l beta subunit from genomic DNA was amplified by PCR. The T594M varian t was detected by single-strand conformational polymorphism analysis o f PCR products and confirmed by DNA sequencing. Findings. 17 (8.3%) of 206 hypertensive participants compared with three (2.1%) of 142 normo tensive partcipants possessed the T594M variant (odds ratio [OR]=4.17 [95% CI 1.12-18.25], p = 0.029). A high proportion of participants wit h 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% nor motensive). However, the association between the T594M variant and hyp ertension persisted after adjustment for sex and body-mass index (Mant el-Haenszel OR=5.52 [1.40-30.61], p = 0.012). Plasma renin activity wa s significantly lower in 13 hypertensive participants with the T594M v ariant (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 beta subunit mutation occurs more frequently in people with hypertensi on than those without. The T594M variant may increase sodium-channel a ctivity and could raise blood pressure in affected people by increasin g renal tubular sodium reabsorption. These findings suggest that the T 594M mutation could be the most common secondary cause of essential hy pertension in black people identified to date.