OBJECTIVE: A common threonine481serine polymorphism (T481S) has been shown in vitro to strongly activate the chloride channel Kb (CLC-Kb) expressed in the kidney, and the 481S allele has been associated with human hypertension. The study aim was to evaluate the association of the T481S polymorphism with blood pressure (BP) levels and the BP progression rate in Swedes. DESIGN AND METHODS: The cardiovascular cohort of the Malmö Diet and Cancer (MDC) study is a population surveyed in 1991-1996 (n=6103, DNA available on n=6055), 53% of whom had also been examined 11 +/- 4.4 years earlier in the Malmö Preventive Project (MPP). Hypertension was defined as having BP above 140/90 mmHg or being on antihypertensive therapy (AHT). Carriers of one or two copies of the 481S allele were compared with T481T homozygotes (noncarriers). RESULTS: Among individuals without AHT in the MDC study (n=4988) there was no difference between carriers (n=1164, 23%) and noncarriers (n=3824, 77%) in systolic BP (139.3 +/- 8.3 vs 139.2 +/- 8.3 mmHg, P = 0.82) or diastolic BP (86.0 +/- 9.1 vs 86.0 +/- 9.2 mmHg, P = 0.95). In subjects free from AHT at the MPP and MDC studies (n=2627) there was no difference between carriers (n=607, 23%) and noncarriers (n=2020, 77%) in progression of systolic BP (2.1 +/- 2.6 vs 2.0 +/- 2.8 mmHg/year, P = 0.72) or diastolic BP (0.57 +/- 1.4 vs 0.58 +/- 1.6 mmHg/year, P = 0.85) from MPP to MDC. Multivariate analysis gave no support of interaction between the CLC-Kb T481S polymorphism, gender, age or body mass index regarding their effect on BP. CONCLUSION: Our data do not support a role of the CLC-Kb T481S polymorphism in BP regulation in Swedes.
The functional variant of the CLC-Kb channel T481S is not associated with blood pressure or hypertension in Swedes
FAVA, Cristiano;MONTAGNANA, Martina;GUIDI, Giancesare;
2007-01-01
Abstract
OBJECTIVE: A common threonine481serine polymorphism (T481S) has been shown in vitro to strongly activate the chloride channel Kb (CLC-Kb) expressed in the kidney, and the 481S allele has been associated with human hypertension. The study aim was to evaluate the association of the T481S polymorphism with blood pressure (BP) levels and the BP progression rate in Swedes. DESIGN AND METHODS: The cardiovascular cohort of the Malmö Diet and Cancer (MDC) study is a population surveyed in 1991-1996 (n=6103, DNA available on n=6055), 53% of whom had also been examined 11 +/- 4.4 years earlier in the Malmö Preventive Project (MPP). Hypertension was defined as having BP above 140/90 mmHg or being on antihypertensive therapy (AHT). Carriers of one or two copies of the 481S allele were compared with T481T homozygotes (noncarriers). RESULTS: Among individuals without AHT in the MDC study (n=4988) there was no difference between carriers (n=1164, 23%) and noncarriers (n=3824, 77%) in systolic BP (139.3 +/- 8.3 vs 139.2 +/- 8.3 mmHg, P = 0.82) or diastolic BP (86.0 +/- 9.1 vs 86.0 +/- 9.2 mmHg, P = 0.95). In subjects free from AHT at the MPP and MDC studies (n=2627) there was no difference between carriers (n=607, 23%) and noncarriers (n=2020, 77%) in progression of systolic BP (2.1 +/- 2.6 vs 2.0 +/- 2.8 mmHg/year, P = 0.72) or diastolic BP (0.57 +/- 1.4 vs 0.58 +/- 1.6 mmHg/year, P = 0.85) from MPP to MDC. Multivariate analysis gave no support of interaction between the CLC-Kb T481S polymorphism, gender, age or body mass index regarding their effect on BP. CONCLUSION: Our data do not support a role of the CLC-Kb T481S polymorphism in BP regulation in Swedes.
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