title: Genetic contribution to C-reactive protein levels in severe obesity.
abstract: Obese individuals are characterized by a chronic, low-grade inflammatory state. Increased levels of C-reactive protein (CRP), a marker of inflammation, have been observed in subjects with the metabolic syndrome. We have previously reported that genes encoding proteins involved in the anti-inflammatory and immune response are differentially expressed in visceral adipose tissue of obese men with or without the metabolic syndrome. Among these genes, the interferon-gamma-inducible protein 30 (IFI30), CD163 molecule (CD163), chemokine (C-X-C motif) ligand 9 (CXCL9) and thymic stromal lymphopoietin (TSLP), were selected for further genetic analyses. The aim of the study was to verify whether IFI30, CD163, CXCL9 and TSLP gene polymorphisms contribute to explain the inter-individual variability of the inflammatory profile of obesity assessed by plasma high-sensitivity CRP concentrations. A total of 1185 severely obese individuals were genotyped for single nucleotide polymorphisms (SNPs) covering most of the sequence-derived genetic variability at the IFI30, CD163, CXCL9 and TSLP gene loci (total of 27 SNPs). Following measurement of plasma CRP levels, subjects were divided into two groups, low vs. high using the median value of plasma CRP levels (8.31 mg/L) as a cutoff point. Genotype frequencies were compared between groups. Associations between genotypes and plasma CRP levels (continuous variable) were also tested after adjustments for age, sex, smoking and BMI. The rs11554159 and rs7125 IFI30 SNPs showed a significant difference in genotype frequencies (p<0.05) between subgroups of low vs. high plasma CRP levels (wild type homozygotes: rs11554159=47% vs. 55%, rs7125=31% vs. 24%, for low vs. high CRP groups, respectively). The association between rs11554159 and CRP levels as a continuous variable remained significant (p=0.004). Both carriers of the GA and AA genotypes demonstrated, on average, a 13% lower CRP levels in comparison with GG homozygotes. No association was observed between SNPs in the CD163, CXCL9 and TSLP genes and CRP levels. The IFI30 rs11554159 polymorphism could partially explain the inter-individual variability observed in the inflammatory profile associated with obesity.
authors.affiliation: Nutraceuticals and Functional Foods Institute (INAF), Laval University, Québec, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Faucher
authors.forename: Frédéric
authors.initials: F
authors.lastname: Guénard
authors.forename: Luigi
authors.initials: L
authors.lastname: Bouchard
authors.forename: Véronique
authors.initials: V
authors.lastname: Garneau
authors.forename: Valérie
authors.initials: V
authors.lastname: Turcot
authors.forename: Alain
authors.initials: A
authors.lastname: Houde
authors.forename: André
authors.initials: A
authors.lastname: Tchernof
authors.forename: Jean
authors.initials: J
authors.lastname: Bergeron
authors.forename: Yves
authors.initials: Y
authors.lastname: Deshaies
authors.forename: Frédéric-Simon
authors.initials: FS
authors.lastname: Hould
authors.forename: Stéfane
authors.initials: S
authors.lastname: Lebel
authors.forename: Picard
authors.initials: P
authors.lastname: Marceau
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis* / Q000276:immunology; D054370:Chemokine CXCL9 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics; D017422:Sequence Analysis, DNA; D000094632:Thymic Stromal Lymphopoietin; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D016207:Cytokines; D011956:Receptors, Cell Surface; D002097:C-Reactive Protein; C056859:IFI30 protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors; D000094632:Thymic Stromal Lymphopoietin