Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: The PROSPER study

Stella Trompet; D. Pons; A. J.M. De Craen; P. Slagboom; J. Shepherd; G. J. Blauw; M. B. Murphy; S. M. Cobbe; E. L.E.M. Bollen; B. M. Buckley; I. Ford; M. Hyland; A. Gaw; P. W. Macfarlane; C. J. Packard; J. Norrie; I. J. Perry; D. J. Stott; B. J. Sweeney; C. Twomey; R. G.J. Westendorp; J. W. Jukema

doi:10.1196/annals.1395.018

Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: The PROSPER study

Stella Trompet, D. Pons, A. J.M. De Craen, P. Slagboom, J. Shepherd, G. J. Blauw, M. B. Murphy, S. M. Cobbe, E. L.E.M. Bollen, B. M. Buckley, I. Ford, M. Hyland, A. Gaw, P. W. Macfarlane, C. J. Packard, J. Norrie, I. J. Perry, D. J. Stott, B. J. Sweeney, C. TwomeyR. G.J. Westendorp, J. W. Jukema

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

47 Scopus citations

Abstract

Proinflammatory cytokines, like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), 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 associationswere 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.

Original language	English
Title of host publication	Biogerontology
Subtitle of host publication	Mechanisms and Interventions
Publisher	Blackwell Publishing Inc.
Pages	189-198
Number of pages	10
ISBN (Print)	1573316792, 9781573316798
DOIs	https://doi.org/10.1196/annals.1395.018
State	Published - Apr 2007
Externally published	Yes

Publication series

Name	Annals of the New York Academy of Sciences
Volume	1100
ISSN (Print)	0077-8923
ISSN (Electronic)	1749-6632

Keywords

Anti-inflammation
Atherosclerosis
Interleukin-10
Stroke

Access to Document

10.1196/annals.1395.018

Cite this

Trompet, S., Pons, D., De Craen, A. J. M., Slagboom, P., Shepherd, J., Blauw, G. J., Murphy, M. B., Cobbe, S. M., Bollen, E. L. E. M., Buckley, B. M., Ford, I., Hyland, M., Gaw, A., Macfarlane, P. W., Packard, C. J., Norrie, J., Perry, I. J., Stott, D. J., Sweeney, B. J., ... Jukema, J. W. (2007). Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: The PROSPER study. In Biogerontology: Mechanisms and Interventions (pp. 189-198). (Annals of the New York Academy of Sciences; Vol. 1100). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1395.018

@inproceedings{a3f061cbc15c4d2881288b6202a53d22,

title = "Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: The PROSPER study",

abstract = "Proinflammatory cytokines, like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), 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 associationswere 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.",

keywords = "Anti-inflammation, Atherosclerosis, Interleukin-10, Stroke",

author = "Stella Trompet and D. Pons and {De Craen}, {A. J.M.} and P. Slagboom and J. Shepherd and Blauw, {G. J.} and Murphy, {M. B.} and Cobbe, {S. M.} and Bollen, {E. L.E.M.} and Buckley, {B. M.} and I. Ford and M. Hyland and A. Gaw and Macfarlane, {P. W.} and Packard, {C. J.} and J. Norrie and Perry, {I. J.} and Stott, {D. J.} and Sweeney, {B. J.} and C. Twomey and Westendorp, {R. G.J.} and Jukema, {J. W.}",

year = "2007",

month = apr,

doi = "10.1196/annals.1395.018",

language = "English",

isbn = "1573316792",

series = "Annals of the New York Academy of Sciences",

publisher = "Blackwell Publishing Inc.",

pages = "189--198",

booktitle = "Biogerontology",

}

Trompet, S, Pons, D, De Craen, AJM, Slagboom, P, Shepherd, J, Blauw, GJ, Murphy, MB, Cobbe, SM, Bollen, ELEM, Buckley, BM, Ford, I, Hyland, M, Gaw, A, Macfarlane, PW, Packard, CJ, Norrie, J, Perry, IJ, Stott, DJ, Sweeney, BJ, Twomey, C, Westendorp, RGJ & Jukema, JW 2007, Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: The PROSPER study. in Biogerontology: Mechanisms and Interventions. Annals of the New York Academy of Sciences, vol. 1100, Blackwell Publishing Inc., pp. 189-198. https://doi.org/10.1196/annals.1395.018

Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: The PROSPER study. / Trompet, Stella; Pons, D.; De Craen, A. J.M. et al.
Biogerontology: Mechanisms and Interventions. Blackwell Publishing Inc., 2007. p. 189-198 (Annals of the New York Academy of Sciences; Vol. 1100).

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

TY - GEN

T1 - Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events

T2 - The PROSPER study

AU - Trompet, Stella

AU - Pons, D.

AU - De Craen, A. J.M.

AU - Slagboom, P.

AU - Shepherd, J.

AU - Blauw, G. J.

AU - Murphy, M. B.

AU - Cobbe, S. M.

AU - Bollen, E. L.E.M.

AU - Buckley, B. M.

AU - Ford, I.

AU - Hyland, M.

AU - Gaw, A.

AU - Macfarlane, P. W.

AU - Packard, C. J.

AU - Norrie, J.

AU - Perry, I. J.

AU - Stott, D. J.

AU - Sweeney, B. J.

AU - Twomey, C.

AU - Westendorp, R. G.J.

AU - Jukema, J. W.

PY - 2007/4

Y1 - 2007/4

N2 - Proinflammatory cytokines, like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), 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 associationswere 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.

AB - Proinflammatory cytokines, like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), 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 associationswere 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.

KW - Anti-inflammation

KW - Atherosclerosis

KW - Interleukin-10

KW - Stroke

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U2 - 10.1196/annals.1395.018

DO - 10.1196/annals.1395.018

M3 - Conference contribution

C2 - 17460178

AN - SCOPUS:34249672701

SN - 1573316792

SN - 9781573316798

T3 - Annals of the New York Academy of Sciences

SP - 189

EP - 198

BT - Biogerontology

PB - Blackwell Publishing Inc.

ER -

Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: The PROSPER study

Abstract

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Keywords

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