The −174G/C polymorphism of IL-6 is useful to screen old subjects at risk for atherosclerosis or to reach successful ageing

Abstract

High levels of IL-6 are coupled with impaired immune efficiency, morbidity and mortality in ageing. Elderly men with GG (C−) genotype in −174 locus of IL-6 promoter are disadvantaged for longevity due to higher IL-6 than CG or CC (C+) carriers. As IL-6 increases in atherosclerosis, the study of the polymorphism of IL-6 may be a useful tool in identifying old subjects at risk for atherosclerosis. Thus, we divided old men into C+ and C− genotypes. Natural killer (NK) cell cytotoxicity, IL-6, IL-10, TNF-α, MTmRNA and zinc ion bioavailability were also evaluated and compared with nonagenarians and old patients affected by carotid stenosis. Old C− patients display, other than elevated IL-6, higher IL-10, TNF-α and MTmRNA coupled with impaired NK cell cytotoxicity and lower zinc ion bioavailability than C+ patients. The same trend is observed in old subjects with C− phenotype. Nonagenarians with C+ genotype show less inflammation, low MTmRNA, satisfactory NK cell cytotoxicity and good zinc bioavailability than long-living individuals with C− genotype. A higher degree of bilateral carotid stenosis is observed in C− patients than in C+ patients (88 vs 52%). Therefore, C− genotype is coupled with chronic inflammation, impaired immune efficiency, low zinc ion bioavailability and high MTmRNA. As such, C− genotype is a risk factor for the appearance of severe atherosclerosis. Thus, the polymorphism of IL-6, together with the analysis of zinc turnover and immune parameters, is of a great clinical relevance in order to genetically identify old subjects at risk in developing severe atherosclerosis and, at the same time, to predict subjects predestined to successful ageing. As a consequence, more convenient therapies may be prepared for a complete recovery.