Research Paper Volume 13, Issue 6 pp 7953—7974

Lifespan extension conferred by mitogen-activated protein kinase kinase kinase 5 (MAP3K5) longevity-associated gene variation is confined to at-risk men with a cardiometabolic disease

Forest plots of mortality risk (hazard ratio and 95% CI), adjusted for age, BMI and glucose at baseline, for men with a CMD and men without a CMD according to genotype of MAP3K5 SNP rs2076260 in each genetic model. (A) major allele homozygote (CC) vs. minor allele carriers (CT+TT). (B) heterozygote disadvantage model, CT vs. CC/TT. It can be seen that in men with a CMD who had the longevity-associated genotype, mortality risk was reduced to normal in that it did not differ significantly from the survival curve in men without a CMD. It should be noted that the HRs in Figure 2 differ slightly from those in Table 1. This is because the HRs in Table 1 were obtained from stratified analyses by diabetes, hypertension, CHD, and any CMD (i.e., were separately estimated by disease status). In Figure 2, we compared the HRs for the 4 groups by CMD and MAP3K5 genotype. The HRs and p-values for pairwise comparisons among the 4 groups were estimated in one Cox model.

Figure 2. Forest plots of mortality risk (hazard ratio and 95% CI), adjusted for age, BMI and glucose at baseline, for men with a CMD and men without a CMD according to genotype of MAP3K5 SNP rs2076260 in each genetic model. (A) major allele homozygote (CC) vs. minor allele carriers (CT+TT). (B) heterozygote disadvantage model, CT vs. CC/TT. It can be seen that in men with a CMD who had the longevity-associated genotype, mortality risk was reduced to normal in that it did not differ significantly from the survival curve in men without a CMD. It should be noted that the HRs in Figure 2 differ slightly from those in Table 1. This is because the HRs in Table 1 were obtained from stratified analyses by diabetes, hypertension, CHD, and any CMD (i.e., were separately estimated by disease status). In Figure 2, we compared the HRs for the 4 groups by CMD and MAP3K5 genotype. The HRs and p-values for pairwise comparisons among the 4 groups were estimated in one Cox model.