IL-32 Promoter SNP rs4786370 Predisposed to Modified Lipoprotein Profiles in Patients with Rheumatoid Arthritis

Michelle S.M.A. Damen¹, Rabia Agca², Suzanne Holewijn³, Jacqueline de Graaf¹, Jéssica C. Dos Santos^1,4, Piet L van Riel⁵, J Fransen⁶, Marieke J.H. Coenen⁷, Mike T. Nurmohamed⁸, M.G. Netea¹, Charles Dinarello⁹, L.A.B. Joosten¹, Bas Heinhuis¹ and Calin Popa¹⁰, ¹Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands, ²Rheumatology, Amsterdam Rheumatology and immunology Center, Location Reade, Amsterdam, Netherlands, ³Rijnstate Ziekenhuis, Arnhem, Netherlands, ⁴Instituto de Patologia Tropical e Saúde Pública, Goiás, Brazil, ⁵Scientific Institute for Quality of Healthcare, Radboud University Medical Center, Nijmegen, Netherlands, ⁶Department of Rheumatolgy, Radboud UMC, Nijmegen, Netherlands, ⁷Human Genetics (855), Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ⁸Rheumatology, Amsterdam Rheumatology and immunology Center, Location VU University Medical Center, Amsterdam, Netherlands, Amsterdam, Netherlands, ⁹Department of Medicine, Division of Infectious Diseases, University of Colorado, Denver, CO, ¹⁰Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Cardiovascular disease, interleukins (IL), Lipids, polymorphism and rheumatoid arthritis (RA)

Session Information

Date: Sunday, November 13, 2016

Title: Genetics, Genomics and Proteomics - Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Patients with a chronic inflammatory disease such as 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 also be linked to the development of atherosclerosis. However the exact mechanism linking IL-32 to CVD still needs to be elucidated.

Methods: Whole blood was obtained from individuals from the NBS cohort and RA patients from 2 independent cohorts to study the influence of a functional genetic variant IL-32 on lipid profiles and CVD risk. DNA was isolated and genotyped for the single nucleotide polymorphism (SNP) rs4786370 in IL-32 using a taqman genotyping assay. Lipid profiles were measured and matched to the specific IL-32 genotypes.

Results: The allelic distribution of the IL-32 promoter SNP 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). This finding was independent of the presence of plaques or previous CVD events in these groups. 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). Within RA patients with a previous CVD event, the LDLc and TC levels were lower compared to RA patients without a previous CVD event, independent of the genotype (p<0.0001).

Conclusion: The rs4786370 promoter polymorphism of IL-32 is equally expressed in all three cohorts. However, this genetic variant has a specific functional effect on the lipid profile of individuals from the NBS cohort and RA patients, resulting in increased HDLc levels. Future studies should focus on the mechanism behind the increase in HDLc in individuals with the IL-32 promoter SNP and its possible protective role against CVD.

Disclosure: M. S. M. A. Damen, None; R. Agca, None; S. Holewijn, None; J. de Graaf, None; J. C. Dos Santos, None; P. L. van Riel, None; J. Fransen, Bristol-Myers Squibb, 2; M. J. H. Coenen, None; M. T. Nurmohamed, None; M. G. Netea, European Research Council, 9; C. Dinarello, None; L. A. B. Joosten, None; B. Heinhuis, None; C. Popa, None.

To cite this abstract in AMA style:

Damen MSMA, Agca R, Holewijn S, de Graaf J, Dos Santos JC, van Riel PL, Fransen J, Coenen MJH, Nurmohamed MT, Netea MG, Dinarello C, Joosten LAB, Heinhuis B, Popa C. IL-32 Promoter SNP rs4786370 Predisposed to Modified Lipoprotein Profiles in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/il-32-promoter-snp-rs4786370-predisposed-to-modified-lipoprotein-profiles-in-patients-with-rheumatoid-arthritis/. Accessed .

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