Human Genetics

, Volume 131, Issue 1, pp 57–66

A polymorphism of the interferon-gamma-inducible protein 30 gene is associated with hyperglycemia in severely obese individuals

  • V. Turcot
  • L. Bouchard
  • G. Faucher
  • A. Tchernof
  • Y. Deshaies
  • L. Pérusse
  • P. Marceau
  • F. S. Hould
  • S. Lebel
  • Marie-Claude Vohl
Original Investigation

DOI: 10.1007/s00439-011-1043-4

Cite this article as:
Turcot, V., Bouchard, L., Faucher, G. et al. Hum Genet (2012) 131: 57. doi:10.1007/s00439-011-1043-4

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.

Abbreviations

BMI

Body mass index

bp

Base pair

CRP

C-reactive protein

CVD

Cardiovascular disease

GILT

Gamma-interferon-inducible lysosomal thiol reductase

GLM

General linear model

HDL

High-density lipoprotein

IDF

International Diabetes Federation

IFI30

Interferon-gamma-inducible protein 30

LD

Linkage disequilibrium

LDL

Low-density lipoprotein

LS

Least square

MAF

Minor allele frequency

MHC

Major histocompatibility complex

MS

Metabolic syndrome

NCEP-ATPIII

National Cholesterol Education Program-Adult Treatment Panel III

qRT-PCR

Quantitative real-time reverse transcriptase polymerase chain reaction

OR

Odds-ratio

SNPs

Single-nucleotide polymorphisms

T2D

Type 2 diabetes

TSS

Translation start site

UTR

Untranslated region

VAT

Visceral adipose tissue

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • V. Turcot
    • 1
    • 2
  • L. Bouchard
    • 3
  • G. Faucher
    • 1
    • 2
  • A. Tchernof
    • 2
  • Y. Deshaies
    • 4
  • L. Pérusse
    • 1
    • 5
  • P. Marceau
    • 4
  • F. S. Hould
    • 4
  • S. Lebel
    • 4
  • Marie-Claude Vohl
    • 1
    • 2
  1. 1.Institute of Nutraceuticals and Functional Foods (INAF), Pavillon des ServicesLaval UniversityQuebecCanada
  2. 2.Molecular Endocrinology and Genomics, CHUQLaval UniversityQuebecCanada
  3. 3.Department of Biochemistry, Faculty of Medicine and Health SciencesUniversity of Sherbrooke, and ECOGENE-21 Research Center, Chicoutimi HospitalQuebecCanada
  4. 4.Quebec Heart and Lung Institute, Faculty of MedicineLaval UniversityQuebecCanada
  5. 5.Department of Preventive MedicineLaval UniversityQuebecCanada

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