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. 2015 Jul 8:12:7.
doi: 10.1186/s12979-015-0034-z. eCollection 2015.

Less functional variants of TLR-1/-6/-10 genes are associated with age

Lutz Hamann  1 , Juozas Kupcinskas  2 , Luis C Berrocal Almanza  1 , Jurgita Skieceviciene  3 , Andre Franke  4 , Ute Nöthlings  5 , Ralf R Schumann  1
Affiliations

Less functional variants of TLR-1/-6/-10 genes are associated with age

Lutz Hamann et al. Immun Ageing. .

Erratum in

Abstract

Background: Determining the prerequisites for healthy aging is a major task in the modern world characterized by a longer lifespan of the individuals. Besides lifestyle and environmental influences genetic factors are involved as shown by several genome-wide association studies. Older individuals are known to have an impaired immune response, a condition recently termed "inflamm-aging". We hypothesize that the induction of this condition in the elderly is influenced by the sensitivity of the innate immune system. Therefore, we investigated genetic variants of the Toll-like receptor (TLR) family, one of the major family of innate immune receptors, for association with age in two cohorts of healthy, disease-free subjects.

Results: According to sex we found a positive association of loss-of-function variants of TLR-1 and -6 with healthy aging with odds ratios of 1.54 in males for TLR-6 (249 S/S), and 1.41, 1.66, and 1.64 in females for TLR-1 prom., TLR-1 (248 S/S), and TLR-1 (602 S/S), respectively. Thus, the presence of these variants increases the probability of achieving healthy old age and indicates that a reduced TLR activity may be beneficial in the elderly.

Conclusions: This is the first report showing an association of TLR variants with age. While a loss of function of an important immune receptor may be a risk factor for acute infections as has been shown previously, in the setting of healthy ageing it appears to be protective, which may relate to "inflamm-aging". These first results should be reproduced in larger trials to confirm this hypothesis.

Keywords: Healthy aging; Inflamm-aging; Innate immunity; Polymorphisms; Toll-like receptors.

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Figures

Fig. 1
Fig. 1
TLR-6/1/10 region on chromosome 4. Arrangement of TLR-6/1/10 and adjacent genes on chromosome 4 and the localization of investigated SNPs
See this image and copyright information in PMC

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