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.
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
authors.forename: Michelle S M A
authors.initials: MS
authors.lastname: Damen
authors.affiliation: Amsterdam Rheumatology immunology Center, Department of Rheumatology, location CU University Medical Center and Reade, Amsterdam, The Netherlands.
authors.forename: Rabia
authors.initials: R
authors.lastname: Agca
authors.affiliation: Rijnstate Ziekenhuis, Arnhem, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Holewijn
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Graaf
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.|Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Brazil.
authors.forename: Jéssica C
authors.initials: JC
authors.lastname: Dos Santos
authors.affiliation: Department of Rheumatology, Bernhoven Ziekenhuis, Uden, The Netherlands.
authors.forename: Piet L
authors.initials: PL
authors.lastname: van Riel
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Fransen
authors.affiliation: Radboud Institute for Health Sciences, Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Marieke J H
authors.initials: MJ
authors.lastname: Coenen
authors.affiliation: Amsterdam Rheumatology immunology Center, Department of Rheumatology, location CU University Medical Center and Reade, Amsterdam, The Netherlands.
authors.forename: Mike T
authors.initials: MT
authors.lastname: Nurmohamed
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.|School of Medicine, Division of infectious diseases, University of Colorado Denver, Aurora, Colorado 80045, United States of America.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Heinhuis
authors.affiliation: Department of Rheumatology, Bernhoven Ziekenhuis, Uden, The Netherlands.|Department of Rheumatology, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.
authors.forename: Calin D
authors.initials: CD
authors.lastname: Popa
mesh_terms: D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011401:Promoter Regions, Genetic
chemical_list: D008076:Cholesterol, HDL; C496971:IL32 protein, human; D007378:Interleukins; D008074:Lipoproteins