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

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.

SUBMITTER: Morris BJ

PROVIDER: S-EPMC5055732 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Morris Brian J BJ Chen Randi R Donlon Timothy A TA Evans Daniel S DS Tranah Gregory J GJ Parimi Neeta N Ehret Georg B GB Newton-Cheh Christopher C Seto Todd T Willcox D Craig DC Masaki Kamal H KH Kamide Kei K Ryuno Hirochika H Oguro Ryosuke R Nakama Chikako C Kabayama Mai M Yamamoto Koichi K Sugimoto Ken K Ikebe Kazunori K Masui Yukie Y Arai Yasumichi Y Ishizaki Tatsuro T Gondo Yasuyuki Y Rakugi Hiromi H Willcox Bradley J BJ

American journal of hypertension 20161101 11

<h4>Background</h4>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).<h4>Methods</h4>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 statisti ...[more]

PMID: 26476085

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Project description:Background: The association between Aldehyde dehydrogenase II (ALDH-2) rs671 polymorphism and essential hypertension (EH) risk or blood pressure (BP) levels remains unclear. Objective: To systematically review the influence of the aldehyde dehydrogenase II rs671 polymorphism on essential hypertension risk and blood pressure levels. Methods: The PubMed, EMbase, Web of Science, Cochrane Library, CNKI and CBM databases were electronically searched to identify case-control or cohort studies published prior to July 2019 that examined the association between the rs671 polymorphism and the risk of essential hypertension or blood pressure levels. A meta-analysis was conducted with Stata 15.1 software. Results: Twenty-two articles were included. Among these articles, 20 incorporated 30 individual studies evaluating the association between the rs671 polymorphism and EH (11,051 hypertensive patients and 15,926 normotensive controls), and 8 incorporated 12 individual studies evaluating the association between the rs671 polymorphism and BP (20,512 subjects). The results of the meta-analysis showed that the mutation of the rs671 polymorphism was associated with a significantly decreased risk of EH in all models: allelic model (OR = 0.80, 95% CI: 0.73-0.87), homozygous model (OR = 0.71, 95% CI: 0.63-0.80), heterozygous model (OR = 0.79, 95% CI: 0.72-0.87), dominant model (OR = 0.79, 95% CI: 0.71-0.87), and recessive model (OR = 0.76, 95% CI: 0.68-0.85). In the stratified analyses, significant associations were found for males, drinkers and population-based studies. Simultaneously, the A carriers had lower SBP (WMD = -1.78, 95% CI: -3.02 to -0.53) and DBP (WMD = -1.09, 95% CI: -1.58 to -0.61) levels than individuals with the GG homozygote. Conclusion: The collective findings of this meta-analysis suggested that the ALDH-2 rs671 polymorphism represented an important genetic marker in the development of hypertension. Considering the overall quality of evidence and the relatively small pooled sample size, more well-conducted high-quality studies are required to verify the above conclusion. Systematic Review Registration Number: PROSPERO (CRD42019129746).

Dataset Information

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

Publications

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

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