Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: the PROSPER study.
Proinflammatory cytokines, like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), are implicated in the development of atherosclerosis. The role of anti-inflammatory cytokines, like IL-10, is largely unknown. We investigated the association of four single nucleotide polymorphisms (SNPs) in the promoter region of the IL-10 gene (4259AG, -1082GA, -592CA, and -2849GA), with coronary and cerebrovascular disease in participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. All associations were assessed with Cox proportional hazards models adjusted for sex, age, pravastatin use, and country. Haplotype analysis of the four SNPs showed a significant association between haplotype 4 (containing the -592A variant allele) and risk of coronary events (P = 0.019). Moreover, analysis of separate SNPs found a significant association between -2849AA carriers with incident stroke (HR (95%CI) 1.50 (1.04-2.17), P value = 0.02). Our study suggests that not only proinflammatory processes contribute to atherosclerosis, but that also anti-inflammatory cytokines may play an important role.
Trompet
S
S
Department of Gerontology and Geriatrics, C-2-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. s.trompet@lumc.nl
Pons
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D
DE Craen
A J M
AJ
Slagboom
P
P
Shepherd
J
J
Blauw
G J
GJ
Murphy
M B
MB
Cobbe
S M
SM
Bollen
E L E M
EL
Buckley
B M
BM
Ford
I
I
Hyland
M
M
Gaw
A
A
Macfarlane
P W
PW
Packard
C J
CJ
Norrie
J
J
Perry
I J
IJ
Stott
D J
DJ
Sweeney
B J
BJ
Twomey
C
C
Westendorp
R G J
RG
Jukema
J W
JW
D000368:Aged; D002561:Cerebrovascular Disorders / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide; D017035:Pravastatin / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012306:Risk; D012307:Risk Factors
D016753:Interleukin-10; D017035:Pravastatin