title: Association Analysis of FOXO3 Longevity Variants With Blood Pressure and Essential Hypertension.
abstract: The minor alleles of 3 FOXO3 single nucleotide polymorphisms (SNPs)- rs2802292 , rs2253310 , and rs2802288 -are associated with human longevity. The aim of the present study was to test these SNPs for association with blood pressure (BP) and essential hypertension (EHT).
  
  
  
  In a primary study involving Americans of Japanese ancestry drawn from the Family Blood Pressure Program II we genotyped 411 female and 432 male subjects aged 40-79 years and tested for statistical association by contingency table analysis and generalized linear models that included logistic regression adjusting for sibling correlation in the data set. Replication of rs2802292 with EHT was attempted in Japanese SONIC study subjects and of each SNP in a meta-analysis of genome-wide association studies of BP in individuals of European ancestry.
  
  
  
  In Americans of Japanese ancestry, women homozygous for the longevity-associated (minor) allele of each FOXO3 SNP had 6mm Hg lower systolic BP and 3mm Hg lower diastolic BP compared with major allele homozygotes (Bonferroni corrected P < 0.05 and >0.05, respectively). Frequencies of minor allele homozygotes were 3.3-3.9% in women with EHT compared with 9.5-9.6% in normotensive women ( P = 0.03-0.04; haplotype analysis P = 0.0002). No association with BP or EHT was evident in males. An association with EHT was seen for the minor allele of rs2802292 in the Japanese SONIC cohort ( P = 0.03), while in European subjects the minor allele of each SNP was associated with higher systolic and diastolic BP.
  
  
  
  Longevity-associated FOXO3 variants may be associated with lower BP and EHT in Japanese women.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Morris
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center , Honolulu , Hawaii.
authors.forename: Randi
authors.initials: R
authors.lastname: Chen
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center , Honolulu , Hawaii.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Donlon
authors.affiliation: California Pacific Medical Center Research Institute , San Francisco , California.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Evans
authors.affiliation: California Pacific Medical Center Research Institute , San Francisco , California.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tranah
authors.affiliation: California Pacific Medical Center Research Institute , San Francisco , California.
authors.forename: Neeta
authors.initials: N
authors.lastname: Parimi
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine , Baltimore , Maryland.
authors.forename: Georg B
authors.initials: GB
authors.lastname: Ehret
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Broad Institute of Harvard and MIT , Boston , Massachusetts.
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.affiliation: Department of Cardiology, The Queen's Medical Center , Honolulu , Hawaii.
authors.forename: Todd
authors.initials: T
authors.lastname: Seto
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii.|Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii.|Department of Human Welfare, Okinawa International University, Okinawa, Japan.
authors.forename: D Craig
authors.initials: DC
authors.lastname: Willcox
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii.|Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii.
authors.forename: Kamal H
authors.initials: KH
authors.lastname: Masaki
authors.affiliation: Department of Health Science and.|Department of Geriatric Medicine and Nephrology, Osaka University, Graduate School of Medicine, Suita, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kamide
authors.affiliation: Department of Health Science and.
authors.forename: Hirochika
authors.initials: H
authors.lastname: Ryuno
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University, Graduate School of Medicine , Suita , Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Oguro
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University, Graduate School of Medicine , Suita , Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nakama
authors.affiliation: Department of Health Science and.
authors.forename: Mai
authors.initials: M
authors.lastname: Kabayama
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University, Graduate School of Medicine , Suita , Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University, Graduate School of Medicine , Suita , Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Department of Prosthodontics, Gerodontology and Oral Rehabilitation, Osaka University Graduate School of Dentistry , Suita , Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ikebe
authors.affiliation: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology , Tokyo , Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Masui
authors.affiliation: Keio University, School of MedicineTokyo , Japan.
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology , Tokyo , Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishizaki
authors.affiliation: Department of Clinical Thanatology and Geriatric Behavioral Science, Osaka University Graduate School of Human Sciences , Suita , Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Gondo
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University, Graduate School of Medicine , Suita , Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.affiliation: Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii.|Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Willcox
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000235:genetics; D001795:Blood Pressure Determination; D000075222:Essential Hypertension / Q000235:genetics; D005260:Female; D000071316:Forkhead Box Protein O3 / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006973:Hypertension; D008136:Longevity; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3