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

Survival curves spanning the period from baseline (1991–1993) to Dec 31, 2019 for men with and men without a CMD according to genotypes of MAP3K5 SNP rs2076260. The survival probabilities were estimated from the Cox proportional hazard model: h(t) = h(t0) * exp(β1*Age + β2*BMI + β3*Glucose + β4*CMD + β5*MAP3K5

Figure 1. Survival curves spanning the period from baseline (1991–1993) to Dec 31, 2019 for men with and men without a CMD according to genotypes of MAP3K5 SNP rs2076260. The survival probabilities were estimated from the Cox proportional hazard model: h(t) = h(t0) * exp(β1*Age + β2*BMI + β3*Glucose + β4*CMD + β5*MAP3K5_xx + β6* (CMD*MAP3K5_xx)), where “xx” is genotype, by fixing age at 75 years, BMI at the mean, 23.5 kg/m2, and glucose at the mean, 113 mg/dL (where β6 is the effect of the interaction of CMD with MAP3K5 genotype on mortality, for CC vs CT/TT, i.e., a recessive model, giving p(β6) = 0.023). (A) Survival curves for men with a CMD vs. men without a CMD for major allele homozygote (CC) vs. minor allele carriers (CT+TT) (p=0.000041 and p=0.95, respectively). (B) Survival curves for men with a CMD vs. men without a CMD for heterozygote disadvantage model, CT vs. CC/TT (p=0.0000059 and p=0.50, respectively, giving p(β6) = 0.057).