Complement factor H 402His variant confers an increased mortality risk in Finnish nonagenarians: the Vitality 90+ study.
Ageing is characterized by chronic low-grade inflammation and the expected lifespan may be affected by several immunological and inflammatory mediators. In this study, we investigated whether the functional Tyr402His polymorphism (rs1061170) on complement factor H (CFH) gene, which is a key inflammatory downregulator, modulates the longevity of 491 nonagenarians in the Vitality 90+ study. Logistic regression analysis and Kaplan-Meier method with the log rank test were used to examine the effect of the CFH Tyr402His polymorphism on 4-year mortality. After follow-up, we observed that risk factor-adjusted mortality was significantly higher among the carriers of CFH 402His allele compared to non-carriers (OR 1.78, 95% CI 1.19-2.67, p=0.005) and that the survival curves of CFH 402His carriers and non-carriers deviated significantly (p=0.016). We propose that the increased mortality is inflammation-related and mediated by aberrant complement regulation by the CFH 402His variant.
Jylhävä
Juulia
J
Department of Microbiology and Immunology, Medical School, University of Tampere, FIN-33014 Tampere, Finland. juulia.jylhava@uta.fi
Eklund
Carita
C
Jylhä
Marja
M
Hervonen
Antti
A
Lehtimäki
Terho
T
Karhunen
Pekka
P
Hurme
Mikko
M
D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000502:physiology; D017242:Complement Factor H / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008136:Longevity; D008297:Male; D011110:Polymorphism, Genetic
D018836:Inflammation Mediators; D017242:Complement Factor H