Abstract P113: Genotypic Effect Of Foxo3 On Lifespan Is Confined To Men With A Cardiometabolic Disorder (hypertension Or Coronary Heart Disease Or Diabetes)

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Brian J Morris
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Genetic Variants ◽  
Survival Curve ◽  
Human Longevity ◽  
Genotypic Difference ◽  
Nucleotide Polymorphisms ◽  
Genotypic Effect ◽  
Cardiometabolic Disorders ◽  
Cardiometabolic Disorder

FOXO3 is a prominent human longevity gene. To date, no-one has examined whether longevity-associated genetic variants of FOXO3 protect against mortality in all individuals, or whether they protect against mortality only in individuals with aging-related diseases. Here, we examined this issue for the first time. We tested 9 representative longevity associated single nucleotide polymorphisms (SNPs) located within a haplotype block of FOXO3 for association with mortality in 3,584 elderly American men of Japanese ancestry. At baseline (1991-1993), 2,512 had either diabetes (n=1,010), coronary heart disease (CHD; n=738), or hypertension (n=1,919), and 1,072 lacked any of these cardiometabolic disorders (CMDs). The men were followed from baseline until Dec 31, 2019. The longevity-associated (minor) alleles of all 9 SNPs were strongly associated with longer lifespan in individuals who had a CMD (covariate-adjusted hazard ratios [HRs] for each SNP: 0.82-0.95 [ P =0.00008 to 0.020]; covariate adjusted haplotype analysis HR=0.81, P =0.0003). For just diabetes, just hypertension, and just CHD, haplotype HRs were 0.77, 0.82 and 0.83 ( P =0.007, 0.0003 and 0.10), respectively. Reduced mortality was strongest for carriers of the minor ( G ) allele of SNP rs2802292 (covariate adjusted HR=0.82, 95% CI 0.75-0.90; P= 0.00008), as were survival curve differences (covariate adjusted Cox proportional hazard model difference, P =0.0002). As expected, men without a CMD outlived men with a CMD (Kaplan-Meier Log-rank chi-squared=24.8, P =0.0001). There was, however, no genotypic difference in lifespan of men who did not have a CMD (haplotype HR 1.02, P = 0.74). We propose that in individuals with a cardiometabolic disorder, longevity-associated genetic variants of FOXO3 enhance resilience mechanisms in cells and tissues to help protect against cardiometabolic stress caused by CMDs, thereby allowing CMD-affected men to live longer than men without the protective variants.

No causal effects of plasma homocysteine levels on the risk of coronary heart disease or acute myocardial infarction: A Mendelian randomization study

2019 ◽  
pp. 204748731989467 ◽  
Author(s):  
Liu Miao ◽  
Guo-Xiong Deng ◽  
Rui-Xing Yin ◽  
Rong-Jun Nie ◽  
Shuo Yang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Mendelian Randomization ◽  
Plasma Homocysteine ◽  
Sensitivity Analyses ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Artery Disease

Background Although many observational studies have shown an association between plasma homocysteine levels and cardiovascular diseases, controversy remains. In this study, we estimated the role of increased plasma homocysteine levels on the etiology of coronary heart disease and acute myocardial infarction. Methods A two-sample Mendelian randomization study on disease was conducted, i.e. “coronary heart disease” ( n = 184,305) and “acute myocardial infarction” ( n = 181,875). Nine single nucleotide polymorphisms, which were genome-wide significantly associated with plasma homocysteine levels in 57,644 subjects from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium genome-wide association study and were known to be associated at p < 5×10–8, were used as an instrumental variable. Results None of the nine single nucleotide polymorphisms were associated with coronary heart disease or acute myocardial infarction ( p > 0.05 for all). Mendelian randomization analysis revealed no causal effects of plasma homocysteine levels, either on coronary heart disease (inverse variance weighted; odds ratio = 1.015, 95% confidence interval = 0.923–1.106, p = 0.752) or on acute myocardial infarction (inverse variance weighted; odds ratio = 1.037, 95% confidence interval = 0.932–1.142, p = 0.499). The results were consistent in sensitivity analyses using the weighted median and Mendelian randomization-Egger methods, and no directional pleiotropy ( p = 0.213 for coronary heart disease and p = 0.343 for acute myocardial infarction) was observed. Sensitivity analyses confirmed that plasma homocysteine levels were not significantly associated with coronary heart disease or acute myocardial infarction. Conclusions The findings from this Mendelian randomization study indicate no causal relationship between plasma homocysteine levels and coronary heart disease or acute myocardial infarction. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.

scholarly journals Coronary Heart Disease and Genetic Variants with Low Phospholipase A2 Activity

2015 ◽  
Vol 372 (3) ◽  
pp. 295-296 ◽  
Author(s):  
Linda M. Polfus ◽  
Richard A. Gibbs ◽  
Eric Boerwinkle
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Phospholipase A2 ◽  
Genetic Variants ◽  
Phospholipase A2 Activity

scholarly journals Genetic Variants at Newly Identified Lipid Loci Are Associated with Coronary Heart Disease in a Chinese Han Population

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27481 ◽  
Author(s):  
Li Zhou ◽  
Hu Ding ◽  
Xiaomin Zhang ◽  
Meian He ◽  
Suli Huang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Genetic Variants ◽  
Chinese Han Population ◽  
Chinese Han ◽  
Han Population

scholarly journals ANALISIS KURVA SURVIVAL KAPLAN MEIER MENGGUNAKAN UJI LOG RANK (Studi Kasus :Pasien Penyakit Jantung Koroner di RSUD Undata Palu)

2018 ◽  
Vol 7 (1) ◽  
pp. 33-42
Author(s):  
Arianti Suhartini ◽  
Rita Rahmawati ◽  
Suparti Suparti
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Survival Curve ◽  
Disease Status ◽  
Lifestyle Changes ◽  
Rank Test ◽  
Self Awareness ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Central Sulawesi

Coronary heart disease is one of the leading causes of death in the world, including Indonesia. Based on doctor-diagnosed interviews, coronary heart disease’s prevalence in Indonesia on 2013 is 0,5% and based on a doctor-diagnosed is 1,5%. Central Sulawesi is ranked first and second for prevalence based on doctor-diagnosed interviews and doctor-diagnosed. The high number of people with coronary heart disease caused by lack of self-awareness in lifestyle changes. One of the parameters used to assess the success of treatment is the probability of survival. Survival analysis is a data analysis where the outcome of the variables studied is the time until an event occurs. This study raised the problem of survival of coronary heart patients at Undata Palu Hospital which is the main referral hospital for Central Sulawesi region. This research uses nonparametric method that is Kaplan Meier and Log Rank Test based on six factors are age, gender, stadium, disease status, complication and status of anemia. Nonparametric methods do not follow a particular distribution for survival time. Kaplan Meier's survival curve will describe the patient's characteristics of survival probability and followed by a Log Rank test to see if there are differences between curves. The result of analysis and discussion based on Log Rank test result showed that the factors of age, sex and disease status differ significantly. Keywords: Coronary heart disease, RSUD Undata Palu, Kaplan Meier analysis, Log Rank test.

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