title: Interaction according to urinary sodium excretion level on the association between ATP2B1 rs17249754 and incident hypertension: the Korean genome epidemiology study.
abstract: OBJECTIVE
  We examined an interaction according to the estimated 24-h urinary sodium excretion on the association between ATP2B1 rs17249754 and incident hypertension.
  
  
  METHODS
  We assessed the incidence of hypertension in 1780 participants aged 45 to 75 years without cardiovascular diseases. DNA genotyping was performed using the Affymetrix Single Nucleotide Polymorphism (SNP) array 5.0. Because of previously reported associations with hypertension in various populations including Koreans, ATP2B1 rs17249754 was determined. Sodium intake was assessed by estimating the 24-h urinary sodium excretion with a Kawasaki formula from a spot urine sample. We utilized Cox proportional hazard models to test an interaction according to urinary sodium excretion on the association between ATP2B1 rs17249754 and incident hypertension.
  
  
  RESULTS
  The incident hypertension was increased as sodium excretion level was increased. We confirmed that the ATP2B1 rs17249754 polymorphism had significant association with hypertension. We found that the association was modified by urinary sodium excretion level (p-value = 0.006); the mutant type (AA allele, previously recognized as a protective allele) with <4 g/day urinary sodium excretion had an inverse association on hypertension compared with the wild types (GG+GA) (HR = 0.39, 95% confidence interval (CI) 0.17-0.90), whereas the mutant type with ≥6 g/day urinary sodium demonstrated a significantly increased risk of hypertension (HR = 1.89, 95% CI 1.05-3.43).
  
  
  CONCLUSIONS
  In this 6-year longitudinal study, our findings suggest that excessive sodium intake estimated from urinary sodium excretion significantly modified the risk of developing hypertension associated with ATP2B1 rs17249754 genetic trait. That is, carriers with ATP2B1 rs17249754 homozygote mutant allele may be at higher risk of hypertension, when they consume excessive sodium intake.
authors.affiliation: a Institute of Human Genomic Study, Department of Internal Medicine, Korea University Ansan Hospital , Ansan , Gyeonggi , South Korea.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Lee
authors.affiliation: b Division of Cardiology , Korea University Ansan Hospital , Ansan , Gyeonggi , South Korea.
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
authors.affiliation: a Institute of Human Genomic Study, Department of Internal Medicine, Korea University Ansan Hospital , Ansan , Gyeonggi , South Korea.|c Department of Internal Medicine , Korea University Ansan Hospital , Ansan , Gyeonggi , South Korea.
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
mesh_terms: D000368:Aged; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D065667:Renal Elimination / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D012964:Sodium / Q000652:urine*; D012982:Sodium, Dietary / Q000378:metabolism*
chemical_list: C506952:ATP2B1 protein, human; D012982:Sodium, Dietary; D012964:Sodium; D053499:Plasma Membrane Calcium-Transporting ATPases
keywords: ATP2B1; gene–diet interaction; hypertension; sodium