Lack of association of IL6R rs2228145 and IL6ST/gp130 rs2228044 gene polymorphisms with cardiovascular disease in patients with rheumatoid arthritis
Interleukin‐6 (IL‐6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL‐6 receptor (IL‐6R). IL‐6 transducer (IL‐6ST/ gp130) is the signal transducing subunit of the IL‐6R. We assessed the influence of the IL6R and the IL6ST/gp130 genes in the r...
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| Published in | Tissue antigens Vol. 78; no. 6; pp. 438 - 441 |
|---|---|
| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford, UK
Blackwell Publishing Ltd
01.12.2011
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0001-2815 1399-0039 1399-0039 |
| DOI | 10.1111/j.1399-0039.2011.01774.x |
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| Abstract | Interleukin‐6 (IL‐6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL‐6 receptor (IL‐6R). IL‐6 transducer (IL‐6ST/ gp130) is the signal transducing subunit of the IL‐6R. We assessed the influence of the IL6R and the IL6ST/gp130 genes in the risk of cardiovascular (CV) disease in RA. For this purpose, 1250 Spanish patients with RA were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional gene polymorphisms. Patients were stratified according to the presence or absence of CV events. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using two surrogate markers of atherosclerosis (flow‐mediated endothelium‐dependent vasodilatation and carotid intima‐media thickness). No significant differences in the genotype and allele frequencies for both gene polymorphisms between patients with and without CV events were observed. It was also the case when values of surrogate markers of atherosclerosis were compared according to IL6R and IL6ST genotype frequencies. In conclusion, our results do not confirm an association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with CV disease in RA. |
|---|---|
| AbstractList | Interleukin‐6 (IL‐6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL‐6 receptor (IL‐6R). IL‐6 transducer (IL‐6ST/ gp130) is the signal transducing subunit of the IL‐6R. We assessed the influence of the
IL6R
and the
IL6ST/gp130
genes in the risk of cardiovascular (CV) disease in RA. For this purpose, 1250 Spanish patients with RA were genotyped for the
IL6R
rs2228145 and
IL6ST/gp130
rs2228044 functional gene polymorphisms. Patients were stratified according to the presence or absence of CV events. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using two surrogate markers of atherosclerosis (flow‐mediated endothelium‐dependent vasodilatation and carotid intima‐media thickness). No significant differences in the genotype and allele frequencies for both gene polymorphisms between patients with and without CV events were observed. It was also the case when values of surrogate markers of atherosclerosis were compared according to
IL6R
and
IL6ST
genotype frequencies. In conclusion, our results do not confirm an association of
IL6R
rs2228145 and
IL6ST/gp130
rs2228044 polymorphisms with CV disease in RA. Interleukin‐6 (IL‐6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL‐6 receptor (IL‐6R). IL‐6 transducer (IL‐6ST/ gp130) is the signal transducing subunit of the IL‐6R. We assessed the influence of the IL6R and the IL6ST/gp130 genes in the risk of cardiovascular (CV) disease in RA. For this purpose, 1250 Spanish patients with RA were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional gene polymorphisms. Patients were stratified according to the presence or absence of CV events. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using two surrogate markers of atherosclerosis (flow‐mediated endothelium‐dependent vasodilatation and carotid intima‐media thickness). No significant differences in the genotype and allele frequencies for both gene polymorphisms between patients with and without CV events were observed. It was also the case when values of surrogate markers of atherosclerosis were compared according to IL6R and IL6ST genotype frequencies. In conclusion, our results do not confirm an association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with CV disease in RA. Interleukin-6 (IL-6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/ gp130) is the signal transducing subunit of the IL-6R. We assessed the influence of the IL6R and the IL6ST/gp130 genes in the risk of cardiovascular (CV) disease in RA. For this purpose, 1250 Spanish patients with RA were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional gene polymorphisms. Patients were stratified according to the presence or absence of CV events. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using two surrogate markers of atherosclerosis (flow-mediated endothelium-dependent vasodilatation and carotid intima-media thickness). No significant differences in the genotype and allele frequencies for both gene polymorphisms between patients with and without CV events were observed. It was also the case when values of surrogate markers of atherosclerosis were compared according to IL6R and IL6ST genotype frequencies. In conclusion, our results do not confirm an association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with CV disease in RA.Interleukin-6 (IL-6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/ gp130) is the signal transducing subunit of the IL-6R. We assessed the influence of the IL6R and the IL6ST/gp130 genes in the risk of cardiovascular (CV) disease in RA. For this purpose, 1250 Spanish patients with RA were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional gene polymorphisms. Patients were stratified according to the presence or absence of CV events. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using two surrogate markers of atherosclerosis (flow-mediated endothelium-dependent vasodilatation and carotid intima-media thickness). No significant differences in the genotype and allele frequencies for both gene polymorphisms between patients with and without CV events were observed. It was also the case when values of surrogate markers of atherosclerosis were compared according to IL6R and IL6ST genotype frequencies. In conclusion, our results do not confirm an association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with CV disease in RA. |
| Author | Fernández-Gutiérrez, B. García-Bermúdez, M. Martín, J. Miranda-Filloy, J. A. Gómez-Vaquero, C. González-Gay, M. A. Llorca, J. Castañeda, S. González-Álvaro, I. González-Juanatey, C. Balsa, A. López-Mejías, R. Pascual-Salcedo, D. Blanco, R. |
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| Cites_doi | 10.1016/j.semarthrit.2008.01.012 10.1016/j.regpep.2007.09.031 10.1002/art.22482 10.1038/ncprheum0338 10.1002/art.21288 10.1096/fj.99-1003rev 10.1016/j.semarthrit.2008.02.001 10.1016/j.atherosclerosis.2008.08.036 10.1016/j.atherosclerosis.2011.07.124 10.1016/j.atherosclerosis.2010.10.052 10.1002/art.1780310302 10.1007/s00296-010-1593-0 10.4049/jimmunol.152.10.4958 10.3899/jrheum.100717 10.1002/art.22814 |
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| References | Rodriguez-Rodriguez L, Gonzalez-Juanatey C, Palomino-Morales R et al. TNFA -308 (rs1800629) polymorphism is associated with a higher risk of cardiovascular disease in patients with rheumatoid arthritis. Atherosclerosis 2011: 216: 125-30. Chung CP, Oeser A, Raggi P et al. Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors. Arthritis Rheum 2005: 52: 3045-53. Mullberg J, Oberthur W, Lottspeich F et al. The soluble human IL-6 receptor. Mutational characterization of the proteolytic cleavage site. J Immunol 1994: 152: 4958-68. Gonzalez-Gay MA, Gonzalez-Juanatey C, Lopez-Diaz MJ et al. HLA-DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardiovascular mortality in patients with rheumatoid arthritis. Arthritis Rheum 2007: 57: 125-32. López-Mejías R, García-Bermúdez M, González-Juanatey C et al. Lack of association between IL6 single nucleotide polymorphisms and cardiovascular disease in Spanish patients with rheumatoid arthritis. Atherosclerosis 2011 (in press). Nishimoto N, Kishimoto T. Interleukin 6. From bench to bedside. Nat Clin Pract Rheumatol 2006: 2: 619-26. Gonzalez-Gay MA, Gonzalez-Juanatey C, Piñeiro A et al. C-reactive protein elevation correlates with accelerated atherogenesis in patients with rheumatoid arthritis. J Rheumatol 2005: 32: 1219-23. Panoulas VF, Stavropoulos-Kalinoglou A, Metsios GS et al. Association of interleukin-6 (IL-6)-174G/C gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis: the role of obesity and smoking. Atherosclerosis 2009: 204: 178-83. Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Martin J, Llorca J. Endothelial dysfunction, carotid intima-media thickness, and accelerated atherosclerosis in rheumatoid arthritis. Semin Arthritis Rheum 2008: 38: 67-70. Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988: 31: 315-24. Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GM. The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J 2001: 15: 43-58. Marinou I, Healy J, Mewar D et al. Association of interleukin-6 and interleukin-10 genotypes with radiographic damage in rheumatoid arthritis is dependent on autoantibody status. Arthritis Rheum 2007: 56: 2549-56. Benrick A, Jirholt P, Wernstedt I et al. A non-conservative polymorphism in the IL-6 signal transducer (IL6ST)/gp130 is associated with myocardial infarction in a hypertensive population. Regul Pept 2008: 146: 189-96. Gonzalez-Juanatey C, Llorca J, Martin J, Gonzalez-Gay MA. Carotid intima-media thickness predicts the development of cardiovascular events in patients with rheumatoid arthritis. Semin Arthritis Rheum 2009: 38: 366-71. Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol 2011: 38: 10-20. Rodríguez-Rodríguez L, Lamas JR, Varadé J et al. Plasma soluble IL-6 receptor concentration in rheumatoid arthritis. Rheumatol Int 2011: 31: 409-13. 2011; 216 2011 1994; 152 2008; 38 2011; 31 2005; 52 2005; 32 2001; 15 2006; 2 2008; 146 1988; 31 2011; 38 2007; 56 2007; 57 2009; 38 2009; 204 e_1_2_4_2_2 e_1_2_4_4_2 e_1_2_4_3_2 e_1_2_4_5_2 e_1_2_4_8_2 e_1_2_4_7_2 e_1_2_4_9_2 Mullberg J (e_1_2_4_13_2) 1994; 152 e_1_2_4_10_2 e_1_2_4_11_2 e_1_2_4_12_2 e_1_2_4_14_2 Gonzalez‐Gay MA (e_1_2_4_6_2) 2005; 32 e_1_2_4_15_2 e_1_2_4_17_2 e_1_2_4_16_2 |
| References_xml | – reference: Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988: 31: 315-24. – reference: Gonzalez-Gay MA, Gonzalez-Juanatey C, Piñeiro A et al. C-reactive protein elevation correlates with accelerated atherogenesis in patients with rheumatoid arthritis. J Rheumatol 2005: 32: 1219-23. – reference: Benrick A, Jirholt P, Wernstedt I et al. A non-conservative polymorphism in the IL-6 signal transducer (IL6ST)/gp130 is associated with myocardial infarction in a hypertensive population. Regul Pept 2008: 146: 189-96. – reference: Rodríguez-Rodríguez L, Lamas JR, Varadé J et al. Plasma soluble IL-6 receptor concentration in rheumatoid arthritis. Rheumatol Int 2011: 31: 409-13. – reference: Rodriguez-Rodriguez L, Gonzalez-Juanatey C, Palomino-Morales R et al. TNFA -308 (rs1800629) polymorphism is associated with a higher risk of cardiovascular disease in patients with rheumatoid arthritis. Atherosclerosis 2011: 216: 125-30. – reference: Chung CP, Oeser A, Raggi P et al. Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors. Arthritis Rheum 2005: 52: 3045-53. – reference: Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol 2011: 38: 10-20. – reference: Mullberg J, Oberthur W, Lottspeich F et al. The soluble human IL-6 receptor. Mutational characterization of the proteolytic cleavage site. J Immunol 1994: 152: 4958-68. – reference: López-Mejías R, García-Bermúdez M, González-Juanatey C et al. Lack of association between IL6 single nucleotide polymorphisms and cardiovascular disease in Spanish patients with rheumatoid arthritis. Atherosclerosis 2011 (in press). – reference: Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Martin J, Llorca J. Endothelial dysfunction, carotid intima-media thickness, and accelerated atherosclerosis in rheumatoid arthritis. Semin Arthritis Rheum 2008: 38: 67-70. – reference: Gonzalez-Juanatey C, Llorca J, Martin J, Gonzalez-Gay MA. Carotid intima-media thickness predicts the development of cardiovascular events in patients with rheumatoid arthritis. Semin Arthritis Rheum 2009: 38: 366-71. – reference: Panoulas VF, Stavropoulos-Kalinoglou A, Metsios GS et al. Association of interleukin-6 (IL-6)-174G/C gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis: the role of obesity and smoking. Atherosclerosis 2009: 204: 178-83. – reference: Nishimoto N, Kishimoto T. Interleukin 6. From bench to bedside. Nat Clin Pract Rheumatol 2006: 2: 619-26. – reference: Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GM. The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J 2001: 15: 43-58. – reference: Gonzalez-Gay MA, Gonzalez-Juanatey C, Lopez-Diaz MJ et al. HLA-DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardiovascular mortality in patients with rheumatoid arthritis. Arthritis Rheum 2007: 57: 125-32. – reference: Marinou I, Healy J, Mewar D et al. Association of interleukin-6 and interleukin-10 genotypes with radiographic damage in rheumatoid arthritis is dependent on autoantibody status. 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| SubjectTerms | Adult Alleles Arteriosclerosis Arthritis, Rheumatoid - complications Arthritis, Rheumatoid - genetics atherosclerosis Atherosclerosis - complications Atherosclerosis - genetics cardiovascular disease Cardiovascular diseases Cytokine Receptor gp130 - genetics Female Gene frequency Gene Frequency - genetics Gene polymorphism genetics Genotype Glycoprotein gp130 Humans IL6R and IL6ST Inflammation Interleukin 6 Interleukin 6 receptors Male Middle Aged Polymorphism, Genetic Receptors, Interleukin-6 - genetics Rheumatoid arthritis Risk Factors Spain Vasodilation |
| Title | Lack of association of IL6R rs2228145 and IL6ST/gp130 rs2228044 gene polymorphisms with cardiovascular disease in patients with rheumatoid arthritis |
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