The -174G/C polymorphism of IL-6 is useful to screen old subjects at risk for atherosclerosis or to reach successful ageing.
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-alpha, 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-alpha 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.
Giacconi
Robertina
R
Immunology Centre (Sect: Nutrition, Immunity and Ageing), Research Department of INRCA, Via Birarelli 8, 60121 Ancona, Italy.
Cipriano
Catia
C
Albanese
Francesco
F
Boccoli
Gianfranco
G
Saba
Vittorio
V
Olivieri
Fabiola
F
Franceschi
Claudio
C
Mocchegiani
Eugenio
E
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000276:immunology; D001682:Biological Availability; D002340:Carotid Artery Diseases / Q000097:blood / Q000235:genetics* / Q000276:immunology; D016893:Carotid Stenosis / Q000235:genetics / Q000473:pathology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D015032:Zinc / Q000097:blood
D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008668:Metallothionein; D015032:Zinc