title: A polymorphism of the interferon-gamma-inducible protein 30 gene is associated with hyperglycemia in severely obese individuals.
abstract: A previous expression profiling of visceral adipose tissue (VAT) revealed that the immune response gene interferon-gamma-inducible protein 30 (IFI30) gene was 1.72-fold more highly expressed in non-diabetic severely obese men with the metabolic syndrome as compared to those without. Given the importance of low-grade inflammation in obesity-related metabolic complications, we hypothesized that variants in the IFI30 gene are associated with cardiovascular disease (CVD) risk factors. A detailed genetic investigation was performed at the IFI30 locus by sequencing its promoter, exons and intron-exon junction boundaries using DNA of 25 severely obese men. Among the 21 sequence-derived single-nucleotide polymorphisms (SNPs), 5 tagged SNPs (covering 100% of the common SNPs identified) were genotyped in two independent samples of severely obese patients (total n = 1,283). Using a multistage experimental design, chi-square analyses and logistic regressions were performed to compare genotype frequencies and compute odds-ratios (OR) for low and high CVD risk groups (dyslipidemia, hyperglycemia/diabetes and hypertension). A significant association was observed with the non-synonymous SNP rs11554159 (p.R76Q), where GA individuals showed lower risk (OR = 0.67; P = 0.0009) for hyperglycemia/diabetes as compared to homozygotes for the major allele (GG). No association was observed between rs11554159 and VAT IFI30 mRNA levels (P = 0.81), and the expression levels were not correlated with fasting plasma glucose levels (P = 0.31) in 112 non-diabetic severely obese women. The localization of rs11554159 near the active site of IFI30 suggests a functional effect of this SNP. This study showed a novel association between rs11554159 (p.R76Q) polymorphism at the IFI30 locus and the risk of hyperglycemia/diabetes in severely obese individuals.
authors.affiliation: Institute of Nutraceuticals and Functional Foods, Pavillon des Services, Laval University, local 2729K, Quebec G1V 0A6, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Turcot
authors.forename: L
authors.initials: L
authors.lastname: Bouchard
authors.forename: G
authors.initials: G
authors.lastname: Faucher
authors.forename: A
authors.initials: A
authors.lastname: Tchernof
authors.forename: Y
authors.initials: Y
authors.lastname: Deshaies
authors.forename: L
authors.initials: L
authors.lastname: Pérusse
authors.forename: P
authors.initials: P
authors.lastname: Marceau
authors.forename: F S
authors.initials: FS
authors.lastname: Hould
authors.forename: S
authors.initials: S
authors.lastname: Lebel
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology / Q000473:pathology; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000209:etiology / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology* / Q000473:pathology; D015810:Linkage Disequilibrium; D008297:Male; D009765:Obesity / Q000150:complications* / Q000235:genetics*; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D012333:RNA, Messenger; C056859:IFI30 protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors