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Am J Hypertens. 2016 Nov 1;29(11):1292-1300. doi: 10.1093/ajh/hpv171.

Association Analysis of FOXO3 Longevity Variants With Blood Pressure and Essential Hypertension.

Author information

1
Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center , Honolulu , Hawaii.
2
California Pacific Medical Center Research Institute , San Francisco , California.
3
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine , Baltimore , Maryland.
4
Massachusetts General Hospital, Harvard Medical School, Broad Institute of Harvard and MIT , Boston , Massachusetts.
5
Department of Cardiology, The Queen's Medical Center , Honolulu , Hawaii.
6
Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, Hawaii.
7
Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii.
8
Department of Human Welfare, Okinawa International University, Okinawa, Japan.
9
Department of Health Science and.
10
Department of Geriatric Medicine and Nephrology, Osaka University, Graduate School of Medicine, Suita, Japan.
11
Department of Geriatric Medicine and Nephrology, Osaka University, Graduate School of Medicine , Suita , Japan.
12
Department of Prosthodontics, Gerodontology and Oral Rehabilitation, Osaka University Graduate School of Dentistry , Suita , Japan.
13
Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology , Tokyo , Japan.
14
Keio University, School of MedicineTokyo , Japan.
15
Department of Clinical Thanatology and Geriatric Behavioral Science, Osaka University Graduate School of Human Sciences , Suita , Japan.

Abstract

BACKGROUND:

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).

METHODS:

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.

RESULTS:

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.

CONCLUSION:

Longevity-associated FOXO3 variants may be associated with lower BP and EHT in Japanese women.

PMID:
26476085
PMCID:
PMC5055732
[Available on 2017-01-01]
DOI:
10.1093/ajh/hpv171
[Indexed for MEDLINE]
Free PMC Article

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