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

^*Corresponding author for this work

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

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: Mechanisms and Interventions
Editors	Suresh I. S. Rattan, Serif Akman
Pages	189-198
Number of pages	10
Volume	1100
DOIs	https://doi.org/10.1196/annals.1395.018
Publication status	Published - Jun 2007

Publication series

Name	Annals of the New York Academy of Sciences
Volume	1100
ISSN (Print)	00778923
ISSN (Electronic)	17496632

Keywords / Materials (for Non-textual outputs)

Anti-inflammation
Atherosclerosis
Interleukin-10
Stroke

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10.1196/annals.1395.018

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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 S. I. S. Rattan, & S. Akman (Eds.), Biogerontology: Mechanisms and Interventions (Vol. 1100, pp. 189-198). (Annals of the New York Academy of Sciences; Vol. 1100). https://doi.org/10.1196/annals.1395.018

@inproceedings{e27c78c701464242baad94228eef7dd2,

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 = jun,

doi = "10.1196/annals.1395.018",

language = "English",

isbn = "1573316792",

volume = "1100",

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

pages = "189--198",

editor = "Rattan, {Suresh I. S. } and Akman, {Serif }",

booktitle = "Biogerontology: Mechanisms and Interventions",

}

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 SIS Rattan & S Akman (eds), Biogerontology: Mechanisms and Interventions. vol. 1100, Annals of the New York Academy of Sciences, vol. 1100, 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. ed. / Suresh I. S. Rattan; Serif Akman. Vol. 1100 2007. p. 189-198 (Annals of the New York Academy of Sciences; Vol. 1100).

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

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.

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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

VL - 1100

T3 - Annals of the New York Academy of Sciences

SP - 189

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BT - Biogerontology: Mechanisms and Interventions

A2 - Rattan, Suresh I. S.

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ER -

Trompet S, Pons D, De Craen AJM, Slagboom P, Shepherd J, Blauw GJ et al. Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: The PROSPER study. In Rattan SIS, Akman S, editors, Biogerontology: Mechanisms and Interventions. Vol. 1100. 2007. p. 189-198. (Annals of the New York Academy of Sciences). doi: 10.1196/annals.1395.018

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

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