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Gene expression markers of age-related inflammation in two human cohorts.

Abstract：

INTRODUCTION:Chronically elevated circulating inflammatory markers are common in older persons but mechanisms are unclear. Many blood transcripts (>800 genes) are associated with interleukin-6 protein levels (IL6) independent of age. We aimed to identify gene transcripts statistically mediating, as drivers or responders, the increasing levels of IL6 protein in blood at older ages. METHODS:Blood derived in-vivo RNA from the Framingham Heart Study (FHS, n=2422, ages 40-92 yrs) and InCHIANTI study (n=694, ages 30-104 yrs), with Affymetrix and Illumina expression arrays respectively (>17,000 genes tested), were tested for statistical mediation of the age-IL6 association using resampling techniques, adjusted for confounders and multiple testing. RESULTS:In FHS, IL6 expression was not associated with IL6 protein levels in blood. 102 genes (0.6% of 17,324 expressed) statistically mediated the age-IL6 association of which 25 replicated in InCHIANTI (including 5 of the 10 largest effect genes). The largest effect gene (SLC4A10, coding for NCBE, a sodium bicarbonate transporter) mediated 19% (adjusted CI 8.9 to 34.1%) and replicated by PCR in InCHIANTI (n=194, 35.6% mediated, p=0.01). Other replicated mediators included PRF1 (perforin, a cytolytic protein in cytotoxic T lymphocytes and NK cells) and IL1B (Interleukin 1 beta): few other cytokines were significant mediators. CONCLUSIONS:This transcriptome-wide study on human blood identified a small distinct set of genes that statistically mediate the age-IL6 association. Findings are robust across two cohorts and different expression technologies. Raised IL6 levels may not derive from circulating white cells in age related inflammation.

journal_name

Exp Gerontol

journal_title

Experimental gerontology

authors

Pilling LC,Joehanes R,Melzer D,Harries LW,Henley W,Dupuis J,Lin H,Mitchell M,Hernandez D,Ying SX,Lunetta KL,Benjamin EJ,Singleton A,Levy D,Munson P,Murabito JM,Ferrucci L

doi

10.1016/j.exger.2015.05.012

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

37-45

eissn

0531-5565

issn

1873-6815

pii

S0531-5565(15)00188-6

journal_volume

70

pub_type

杂志文章,多中心研究

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