beta-Adducin polymorphisms, blood pressure, and sodium excretion in three European populations.
The associations of the beta-adducin C1797T polymorphism with blood pressure (BP) and various indexes of sodium homeostasis were investigated in 388 men and 456 women, aged 18 to 60 years, recruited from three European populations (Cracow, Poland, n = 300; Novosibirsk, Russian Federation, n = 274; Mirano, Italy; n = 270). Phenotypes included 24-h ambulatory BP and urinary excretion of electrolytes and aldosterone. Subjects were genotyped for the beta-adducin polymorphism. Both a population-based association study and a family-based analysis were performed. Urinary sodium excretion was higher in Cracow than in Mirano (241 v 185 mmol/24 h, P <.05) and intermediate in Novosibirsk (206 mmol/24 h). The beta-adducin T allele (15.2% v 9.1%, P <.0001) was more prevalent in Mirano than in the two Slavic centers. In both population-based and family-based association analyses, there was significant heterogeneity between Slavic and Italian subjects in the phenotype-genotype relationships with beta-adducin. In the Slavic centers, 24-h systolic BP was higher in T allele carriers than in CC homozygotes (122.3 v 119.7 mm Hg, P =.03), whereas this was not the case in Mirano (121.8 v 122.9 mm Hg, P =.42). In Slavic (212.6 v 233.1 mmol/24 h) as well as in Italian (166.1 v 191.5 mmol/24 h) participants, 24-h sodium excretion was lower (P =.01) in T allele carriers than in CC homozygotes. These results were confirmed in the family-based analysis of offspring using a quantitative transmission disequilibrium test. In conclusion, the frequency of the beta-adducin T allele and salt intake differ across European populations. Thus, both variation in genetic background and salt intake may explain the observed heterogeneity in the phenotype-genotype relationships. Genetic determinants of complex quantitative traits such as BP can only be investigated within their epidemiologic context.
Tikhonoff
Valérie
V
Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, University of Leuven, Leuven, Belgium. valerie.tikhonoff@unipd.it
Kuznetsova
Tatiana
T
Stolarz
Katarzyna
K
Bianchi
Giuseppe
G
Casiglia
Edoardo
E
Kawecka-Jaszcz
Kalina
K
Nikitin
Yuri
Y
Tizzone
Laura
L
Wang
Ji Guang
JG
Staessen
Jan A
JA
D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000235:genetics*; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics* / Q000652:urine; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D015995:Prevalence; D012982:Sodium, Dietary / Q000493:pharmacokinetics* / Q000652:urine; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D012982:Sodium, Dietary; D000099291:Adducins