Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein

Mark Adrian Vickers, F. R. Green, B. M. Mayosi, M. Lathrop, PJ. Ratcliffe, HC. Watkins, B. Keavney, C. Terry, C. Julier

Research output: Contribution to journalArticle

223 Citations (Scopus)

Abstract

Objective: Baseline concentrations of plasma C-reactive protein (CRP) are associated with coronary heart disease. Interleukin-6 (IL-6) regulates CRP gene expression; a promoter polymorphism (-174G/C) of the JL-6 gene has been shown to influence IL-6 transcription but the relationship between genotype at this polymorphism and circulating levels of inflammatory markers remains unclear. We hypothesised that plasma CRP would be a heritable phenotype that would be influenced by genotype at this polymorphism. Methods: We measured baseline plasma CRP and determined genotypes at the -174G/C polymorphism of the IL-6 gene in 588 members of 98 nuclear families. The heritability of plasma CRP and the association of plasma CRP with genotype were determined using variance components methods. Results: Baseline CRP levels were highly heritable (h(2) =0.39, P<0.0000001). Presence of the -174C allele was associated with higher baseline CRP levels, both in the whole population (P=0.01), and in the founders only (n=128, P=0.001). Family-based analyses confirmed the association (P=0.02) suggesting that it arises from chromosomal proximity or identity of the typed polymorphism with a genetic variant influencing baseline CRP levels. Conclusions: Baseline plasma CRP is a significantly heritable cardiovascular risk factor. Levels are associated with genotype at the -174G/C polymorphism of the IL-6 gene. (C) 2002 Elsevier Science B.V. All rights reserved.

Original languageEnglish
Pages (from-to)1029-1034
Number of pages5
JournalCardiovascular Research
Volume53
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • atherosclerosis
  • cytokines
  • epidemiology
  • infection/inflammation
  • sequence (DNA/RNA/prot)
  • CIRCULATING INTERLEUKIN-6
  • LINKAGE ANALYSIS
  • INFLAMMATION
  • DISEASE
  • DETERMINANTS
  • VARIABILITY
  • FIBRINOGEN
  • MARKERS
  • TRAITS
  • IL-6

Cite this

Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. / Vickers, Mark Adrian; Green, F. R.; Mayosi, B. M.; Lathrop, M.; Ratcliffe, PJ.; Watkins, HC.; Keavney, B.; Terry, C.; Julier, C.

In: Cardiovascular Research, Vol. 53, No. 4, 2002, p. 1029-1034.

Research output: Contribution to journalArticle

Vickers, MA, Green, FR, Mayosi, BM, Lathrop, M, Ratcliffe, PJ, Watkins, HC, Keavney, B, Terry, C & Julier, C 2002, 'Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein', Cardiovascular Research, vol. 53, no. 4, pp. 1029-1034. https://doi.org/10.1016/S0008-6363(01)00534-X
Vickers, Mark Adrian ; Green, F. R. ; Mayosi, B. M. ; Lathrop, M. ; Ratcliffe, PJ. ; Watkins, HC. ; Keavney, B. ; Terry, C. ; Julier, C. / Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. In: Cardiovascular Research. 2002 ; Vol. 53, No. 4. pp. 1029-1034.
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abstract = "Objective: Baseline concentrations of plasma C-reactive protein (CRP) are associated with coronary heart disease. Interleukin-6 (IL-6) regulates CRP gene expression; a promoter polymorphism (-174G/C) of the JL-6 gene has been shown to influence IL-6 transcription but the relationship between genotype at this polymorphism and circulating levels of inflammatory markers remains unclear. We hypothesised that plasma CRP would be a heritable phenotype that would be influenced by genotype at this polymorphism. Methods: We measured baseline plasma CRP and determined genotypes at the -174G/C polymorphism of the IL-6 gene in 588 members of 98 nuclear families. The heritability of plasma CRP and the association of plasma CRP with genotype were determined using variance components methods. Results: Baseline CRP levels were highly heritable (h(2) =0.39, P<0.0000001). Presence of the -174C allele was associated with higher baseline CRP levels, both in the whole population (P=0.01), and in the founders only (n=128, P=0.001). Family-based analyses confirmed the association (P=0.02) suggesting that it arises from chromosomal proximity or identity of the typed polymorphism with a genetic variant influencing baseline CRP levels. Conclusions: Baseline plasma CRP is a significantly heritable cardiovascular risk factor. Levels are associated with genotype at the -174G/C polymorphism of the IL-6 gene. (C) 2002 Elsevier Science B.V. All rights reserved.",
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T1 - Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein

AU - Vickers, Mark Adrian

AU - Green, F. R.

AU - Mayosi, B. M.

AU - Lathrop, M.

AU - Ratcliffe, PJ.

AU - Watkins, HC.

AU - Keavney, B.

AU - Terry, C.

AU - Julier, C.

PY - 2002

Y1 - 2002

N2 - Objective: Baseline concentrations of plasma C-reactive protein (CRP) are associated with coronary heart disease. Interleukin-6 (IL-6) regulates CRP gene expression; a promoter polymorphism (-174G/C) of the JL-6 gene has been shown to influence IL-6 transcription but the relationship between genotype at this polymorphism and circulating levels of inflammatory markers remains unclear. We hypothesised that plasma CRP would be a heritable phenotype that would be influenced by genotype at this polymorphism. Methods: We measured baseline plasma CRP and determined genotypes at the -174G/C polymorphism of the IL-6 gene in 588 members of 98 nuclear families. The heritability of plasma CRP and the association of plasma CRP with genotype were determined using variance components methods. Results: Baseline CRP levels were highly heritable (h(2) =0.39, P<0.0000001). Presence of the -174C allele was associated with higher baseline CRP levels, both in the whole population (P=0.01), and in the founders only (n=128, P=0.001). Family-based analyses confirmed the association (P=0.02) suggesting that it arises from chromosomal proximity or identity of the typed polymorphism with a genetic variant influencing baseline CRP levels. Conclusions: Baseline plasma CRP is a significantly heritable cardiovascular risk factor. Levels are associated with genotype at the -174G/C polymorphism of the IL-6 gene. (C) 2002 Elsevier Science B.V. All rights reserved.

AB - Objective: Baseline concentrations of plasma C-reactive protein (CRP) are associated with coronary heart disease. Interleukin-6 (IL-6) regulates CRP gene expression; a promoter polymorphism (-174G/C) of the JL-6 gene has been shown to influence IL-6 transcription but the relationship between genotype at this polymorphism and circulating levels of inflammatory markers remains unclear. We hypothesised that plasma CRP would be a heritable phenotype that would be influenced by genotype at this polymorphism. Methods: We measured baseline plasma CRP and determined genotypes at the -174G/C polymorphism of the IL-6 gene in 588 members of 98 nuclear families. The heritability of plasma CRP and the association of plasma CRP with genotype were determined using variance components methods. Results: Baseline CRP levels were highly heritable (h(2) =0.39, P<0.0000001). Presence of the -174C allele was associated with higher baseline CRP levels, both in the whole population (P=0.01), and in the founders only (n=128, P=0.001). Family-based analyses confirmed the association (P=0.02) suggesting that it arises from chromosomal proximity or identity of the typed polymorphism with a genetic variant influencing baseline CRP levels. Conclusions: Baseline plasma CRP is a significantly heritable cardiovascular risk factor. Levels are associated with genotype at the -174G/C polymorphism of the IL-6 gene. (C) 2002 Elsevier Science B.V. All rights reserved.

KW - atherosclerosis

KW - cytokines

KW - epidemiology

KW - infection/inflammation

KW - sequence (DNA/RNA/prot)

KW - CIRCULATING INTERLEUKIN-6

KW - LINKAGE ANALYSIS

KW - INFLAMMATION

KW - DISEASE

KW - DETERMINANTS

KW - VARIABILITY

KW - FIBRINOGEN

KW - MARKERS

KW - TRAITS

KW - IL-6

U2 - 10.1016/S0008-6363(01)00534-X

DO - 10.1016/S0008-6363(01)00534-X

M3 - Article

VL - 53

SP - 1029

EP - 1034

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 4

ER -