Journal of Human Hypertension (2001) 15, 425–430  2001 Nature Publishing Group All rights reserved 0950-9240/01 $15.00 www.nature.com/jhh ORIGINAL ARTICLE T594M and G442V polymorphisms of the sodium channel  subunit and hypertension in a black population YB Dong 1,2 , HD Zhu 1 , EH Baker 1 , GA Sagnella 1 , GA MacGregor 1 , ND Carter 2 , PD Wicks 1,3 , DG Cook 3 and FP Cappuccio 4 Departments of 1 Physiological Medicine, 2 Child Health, 3 Public Health Sciences, 4 General Practice & Primary Care, St George’s Hospital Medical School, London, UK Polymorphisms of the epithelial sodium channel may raise blood pressure by increasing renal sodium reab- sorption. This study examines frequency distributions and associations with hypertension of the T594M and of the G442V polymorphisms of the  subunit of the epi- thelial sodium channel in a population-based sample. We studied a stratified random sample of 459 subjects (279 women), aged 40–59 years, of black African origin from general practices’ lists within a defined area of South London. All were first generation immigrants. The polymorphic variants were detected using single strand conformational polymorphism technique (SSCP). The prevalence of hypertension (BP 160 and/or 95 mm Hg or on drug therapy) was 43%; of these, 76% were on drug therapy. The main analysis was carried out by three ordered blood pressure categories (I to III) accord- Keywords: genetics; epidemiology; black people of African origin; sodium channel Introduction Hypertension is common in black populations of African descent living in urbanised environments. 1 It is a particular problem in Africans and Caribbeans living in the United Kingdom 1,2 with stroke and end- stage renal failure being the major causes of death and disability. 3–6 In a recent population-based sur- vey of cardiovascular risk factors in ethnic minority groups we found that nearly 50% of middle-aged black people (both West Africans and Afro- Caribbeans) had high blood pressure requiring treat- ment. 2–7 High blood pressure in blacks is associated with low plasma renin activity, an index of sodium reten- tion and volume expansion, and appears to be more Correspondence: Dr GA Sagnella (Physiological Medicine) or Professor FP Cappuccio (General Practice and Primary Care), St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK E-mail: g.sagnellasghms.ac.uk or f.cappucciosghms.ac.uk Received 13 July 2000; revised and accepted 27 November 2000 ing to increasing blood pressure and presence or absence of drug therapy. The frequency of the 594M variant (heterozygotes and homozygotes) was 4.6%; the frequency of the 442V variant was higher (27.0%). The frequency of the 594M variant increased with increasing blood pressure category (P  0.05) and was more com- mon in hypertensives than normotensives. By contrast the frequency of the 442V variant did not vary across increasing blood pressure categories (P  0.62). No gender difference was observed. Adjustment for age, sex and body mass index did not alter these findings. These results suggest that the 594M variant may con- tribute to high blood pressure in black people of African origin whereas the G442V polymorphism is unlikely to influence blood pressure in this population. Journal of Human Hypertension (2001) 15, 425–430 sensitive to changes in sodium intake. 8 Previous studies have shown that black people have a slower sodium excretion in response to intravenous sodium infusion suggesting the possibility of a defect in the control of renal sodium excretion. Moreover, there is now evidence of a strong heritable component of salt-sensitivity in blacks. 9 These observations there- fore suggest the possibility of a molecular defect in renal sodium handling. Similarities in some phenotypic expressions between hypertension in blacks and patients with Liddle’s syndrome, 10 a monogenic form of hyperten- sion, have suggested that abnormalities of the distal tubular epithelial sodium channel—a major regu- lator of the overall control of sodium balance—may underlie the development of high blood pressure in blacks. 11 A number of variants of the sodium chan- nel  subunit coding sequences have been identified in subjects with hypertension. 12–14 These lead to a single amino acid change rather than a major trunc- ation as seen in Liddle’s mutations and are much more frequent in blacks than in whites, especially the most commonly identified T594M and G442V polymorphisms. 12