Research Paper Volume 13, Issue 11 pp 14745—14767

Association of growth hormone receptor gene variant with longevity in men is due to amelioration of increased mortality risk from hypertension

Survival curves spanning the period from baseline (1991–1993) to Dec 31, 2019 for subjects with and without hypertension according to genotypes of GHR SNP rs4130113. The survival probabilities were estimated from the Cox proportional hazard model: h(t) = h(t0) * exp(β1*Age + β2*BMI + β3*glucose + β4*hypertension + β5*GHR

Figure 1. Survival curves spanning the period from baseline (1991–1993) to Dec 31, 2019 for subjects with and without hypertension according to genotypes of GHR SNP rs4130113. The survival probabilities were estimated from the Cox proportional hazard model: h(t) = h(t0) * exp(β1*Age + β2*BMI + β3*glucose + β4*hypertension + β5*GHR_AG + β6* (hypertension*GHR_ AG)), 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 hypertension with GHR genotype on mortality, for AG vs AA/GG, i.e., a heterozygote disadvantage model, giving p(β6) = 0.0004). Survival curves of AG vs. AA/GG for hypertensive subjects and subjects without hypertension (p = 0.0003 and p = 0.14, respectively). In men with hypertension who had the longevity-associated genotype AA and those with the GG genotype, the mortality risk was reduced to a level not significantly different from subjects without hypertension (hypertensive AA/GG vs. normotensive AA/GG: p = 0.20; hypertensive AA/GG vs normotensive AG: p = 0.78).