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The W allele of the G460W polymorphism in the adducin-1 gene has been occasionally associated with increased blood pressure (BP). The aim of this study was to test whether the G460W variant is associated with BP levels and BP progression rate and whether G460W associations with BP are affected by sex, body mass index (BMI), or age.The G460W polymorphism was genotyped in the population-based Malmö Diet and Cancer-cardiovascular arm (MDC-CVA; n = 6103), of whom 53% had also been examined 11 ± 4.4 years earlier in the Malmö Preventive Project (MPP).Among subjects without antihypertensive treatment (AHT) in the MDC-CVA (n = 5009), there was no difference between carriers (38%) and noncarriers (62%) of the W allele in systolic BP (139.2 ± 18.2 v 139.2 ± 18.5 mm Hg; P = .99) or diastolic BP (85.9 ± 9.1 v 86.1 ± 9.2 mm Hg; P = .49). In subjects free from AHT in the MPP and MDC (n = 2637) there was no difference between carriers (38%) and noncarriers (62%) in progression of systolic BP (2.0 ± 2.5 v 2.0 ± 2.7 mm Hg/year; P = .45) or diastolic BP (0.59 ± 1.6 v 0.56 ± 1.5 mm Hg/year; P = .66) from MPP to MDC. At MDC-CVA BP was influenced by interaction between the G460W and BMI (P = .02 for systolic BP and P = .002 for diastolic BP) and by interaction between G460W and sex (P = .03 for systolic BP and P = .02 for diastolic BP), a result further confirmed by stratified analysis showing that female carriers of the W allele belonging to the upper tertile of BMI had increased systolic BP (146.1 ± 18.6 v 141.2 ± 18.6 mm Hg; P < .001), diastolic BP (88.7 ± 8.7 v 86.1 ± 8.7 mm Hg; P < .001), and prevalence of hypertension (72.5% v 61.8 %; P = .001).Our data suggest that the G460W polymorphism influences BP when BMI and sex are taken into account. Am J Hypertens 2007;20: 981-989 © 2007 American Journal of Hypertension, Ltd.