IL-32 promoter SNP rs4786370 predisposes to modified lipoprotein profiles in patients with rheumatoid arthritis

Michelle S M A Damen; Rabia Agca; Suzanne Holewijn; Jacqueline de Graaf; Jéssica C Dos Santos; Piet L van Riel; Jaap Fransen; Marieke J H Coenen; Mike T Nurmohamed; Mihai G Netea; Charles A Dinarello; Leo A B Joosten; Bas Heinhuis; Calin D Popa

doi:https://doi.org/10.1038/srep41629

IL-32 promoter SNP rs4786370 predisposes to modified lipoprotein profiles in patients with rheumatoid arthritis

Michelle S M A Damen, Rabia Agca, Suzanne Holewijn, Jacqueline de Graaf, Jéssica C Dos Santos, Piet L van Riel, Jaap Fransen, Marieke J H Coenen, Mike T Nurmohamed, Mihai G Netea, Charles A Dinarello, Leo A B Joosten, Bas Heinhuis, Calin D Popa

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Abstract

Patients with rheumatoid arthritis (RA) are at higher risk of developing cardiovascular diseases (CVD). Interleukin (IL)-32 has previously been shown to be involved in the pathogenesis of RA and might be linked to the development of atherosclerosis. However, the exact mechanism linking IL-32 to CVD still needs to be elucidated. The influence of a functional genetic variant of IL-32 on lipid profiles and CVD risk was therefore studied in whole blood from individuals from the NBS cohort and RA patients from 2 independent cohorts. Lipid profiles were matched to the specific IL-32 genotypes. Allelic distribution was similar in all three groups. Interestingly, significantly higher levels of high density lipoprotein cholesterol (HDLc) were observed in individuals from the NBS cohort and RA patients from the Nijmegen cohort homozygous for the C allele (p = 0.0141 and p = 0.0314 respectively). In contrast, the CC-genotype was associated with elevated low density lipoprotein cholesterol (LDLc) and total cholesterol (TC) in individuals at higher risk for CVD (plaque positive) (p = 0.0396; p = 0.0363 respectively). Our study shows a functional effect of a promoter single-nucleotide polymorphism (SNP) in IL32 on lipid profiles in RA patients and individuals, suggesting a possible protective role of this SNP against CVD.

Original language	English
Pages (from-to)	41629
Journal	Scientific reports
Volume	7
DOIs	https://doi.org/10.1038/srep41629
Publication status	Published - 30 Jan 2017

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Journal Article

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https://doi.org/10.1038/srep41629

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Damen, M. S. M. A., Agca, R., Holewijn, S., de Graaf, J., Dos Santos, J. C., van Riel, P. L., Fransen, J., Coenen, M. J. H., Nurmohamed, M. T., Netea, M. G., Dinarello, C. A., Joosten, L. A. B., Heinhuis, B., & Popa, C. D. (2017). IL-32 promoter SNP rs4786370 predisposes to modified lipoprotein profiles in patients with rheumatoid arthritis. Scientific reports, 7, 41629. https://doi.org/10.1038/srep41629

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title = "IL-32 promoter SNP rs4786370 predisposes to modified lipoprotein profiles in patients with rheumatoid arthritis",

abstract = "Patients with rheumatoid arthritis (RA) are at higher risk of developing cardiovascular diseases (CVD). Interleukin (IL)-32 has previously been shown to be involved in the pathogenesis of RA and might be linked to the development of atherosclerosis. However, the exact mechanism linking IL-32 to CVD still needs to be elucidated. The influence of a functional genetic variant of IL-32 on lipid profiles and CVD risk was therefore studied in whole blood from individuals from the NBS cohort and RA patients from 2 independent cohorts. Lipid profiles were matched to the specific IL-32 genotypes. Allelic distribution was similar in all three groups. Interestingly, significantly higher levels of high density lipoprotein cholesterol (HDLc) were observed in individuals from the NBS cohort and RA patients from the Nijmegen cohort homozygous for the C allele (p = 0.0141 and p = 0.0314 respectively). In contrast, the CC-genotype was associated with elevated low density lipoprotein cholesterol (LDLc) and total cholesterol (TC) in individuals at higher risk for CVD (plaque positive) (p = 0.0396; p = 0.0363 respectively). Our study shows a functional effect of a promoter single-nucleotide polymorphism (SNP) in IL32 on lipid profiles in RA patients and individuals, suggesting a possible protective role of this SNP against CVD.",

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author = "Damen, {Michelle S M A} and Rabia Agca and Suzanne Holewijn and {de Graaf}, Jacqueline and {Dos Santos}, {J{\'e}ssica C} and {van Riel}, {Piet L} and Jaap Fransen and Coenen, {Marieke J H} and Nurmohamed, {Mike T} and Netea, {Mihai G} and Dinarello, {Charles A} and Joosten, {Leo A B} and Bas Heinhuis and Popa, {Calin D}",

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Damen, MSMA, Agca, R, Holewijn, S, de Graaf, J, Dos Santos, JC, van Riel, PL, Fransen, J, Coenen, MJH, Nurmohamed, MT, Netea, MG, Dinarello, CA, Joosten, LAB, Heinhuis, B & Popa, CD 2017, 'IL-32 promoter SNP rs4786370 predisposes to modified lipoprotein profiles in patients with rheumatoid arthritis', Scientific reports, vol. 7, pp. 41629. https://doi.org/10.1038/srep41629

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T1 - IL-32 promoter SNP rs4786370 predisposes to modified lipoprotein profiles in patients with rheumatoid arthritis

AU - Damen, Michelle S M A

AU - Agca, Rabia

AU - Holewijn, Suzanne

AU - de Graaf, Jacqueline

AU - Dos Santos, Jéssica C

AU - van Riel, Piet L

AU - Fransen, Jaap

AU - Coenen, Marieke J H

AU - Nurmohamed, Mike T

AU - Netea, Mihai G

AU - Dinarello, Charles A

AU - Joosten, Leo A B

AU - Heinhuis, Bas

AU - Popa, Calin D

PY - 2017/1/30

Y1 - 2017/1/30

N2 - Patients with rheumatoid arthritis (RA) are at higher risk of developing cardiovascular diseases (CVD). Interleukin (IL)-32 has previously been shown to be involved in the pathogenesis of RA and might be linked to the development of atherosclerosis. However, the exact mechanism linking IL-32 to CVD still needs to be elucidated. The influence of a functional genetic variant of IL-32 on lipid profiles and CVD risk was therefore studied in whole blood from individuals from the NBS cohort and RA patients from 2 independent cohorts. Lipid profiles were matched to the specific IL-32 genotypes. Allelic distribution was similar in all three groups. Interestingly, significantly higher levels of high density lipoprotein cholesterol (HDLc) were observed in individuals from the NBS cohort and RA patients from the Nijmegen cohort homozygous for the C allele (p = 0.0141 and p = 0.0314 respectively). In contrast, the CC-genotype was associated with elevated low density lipoprotein cholesterol (LDLc) and total cholesterol (TC) in individuals at higher risk for CVD (plaque positive) (p = 0.0396; p = 0.0363 respectively). Our study shows a functional effect of a promoter single-nucleotide polymorphism (SNP) in IL32 on lipid profiles in RA patients and individuals, suggesting a possible protective role of this SNP against CVD.

AB - Patients with rheumatoid arthritis (RA) are at higher risk of developing cardiovascular diseases (CVD). Interleukin (IL)-32 has previously been shown to be involved in the pathogenesis of RA and might be linked to the development of atherosclerosis. However, the exact mechanism linking IL-32 to CVD still needs to be elucidated. The influence of a functional genetic variant of IL-32 on lipid profiles and CVD risk was therefore studied in whole blood from individuals from the NBS cohort and RA patients from 2 independent cohorts. Lipid profiles were matched to the specific IL-32 genotypes. Allelic distribution was similar in all three groups. Interestingly, significantly higher levels of high density lipoprotein cholesterol (HDLc) were observed in individuals from the NBS cohort and RA patients from the Nijmegen cohort homozygous for the C allele (p = 0.0141 and p = 0.0314 respectively). In contrast, the CC-genotype was associated with elevated low density lipoprotein cholesterol (LDLc) and total cholesterol (TC) in individuals at higher risk for CVD (plaque positive) (p = 0.0396; p = 0.0363 respectively). Our study shows a functional effect of a promoter single-nucleotide polymorphism (SNP) in IL32 on lipid profiles in RA patients and individuals, suggesting a possible protective role of this SNP against CVD.

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DO - https://doi.org/10.1038/srep41629

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C2 - 28134327

SN - 2045-2322

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JO - Scientific reports

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