G-1 Appeal Activity in the Public Assistance Programs, October 2005

G-1 Appeal Activity in the Public Assistance Programs - October 2005

G-1 Appeal Activity in the Public Assistance Programs, November 2005

G-1 - Appeal Activity in the Public Assistance - November, 2005

IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction.

Approximately 3% of the world population is chronically infected with the hepatitis C virus (HCV), with potential development of cirrhosis and hepatocellular carcinoma. Despite the availability of new antiviral agents, treatment remains suboptimal. Genome-wide association studies (GWAS) identified rs12979860, a polymorphism nearby IL28B, as an important predictor of HCV clearance. We report the identification of a novel TT/-G polymorphism in the CpG region upstream of IL28B, which is a better predictor of HCV clearance than rs12979860. By using peripheral blood mononuclear cells (PBMCs) from individuals carrying different allelic combinations of the TT/-G and rs12979860 polymorphisms, we show that induction of IL28B and IFN-γ-inducible protein 10 (IP-10) mRNA relies on TT/-G, but not rs12979860, making TT/-G the only functional variant identified so far. This novel step in understanding the genetic regulation of IL28B may have important implications for clinical practice, as the use of TT/G genotyping instead of rs12979860 would improve patient management.

Carte muette de France : autorisée par l'université / Lithographie de F.G. Levrault

Échelle(s) : [ca 1: 1 418 000], échelle de 20 myriamètres [= 14,1 cm]

G-1 Appeal Activity in the Public Assistance Programs, December 2005

Appeal Activity in the Public Assistance Programs - December 2005

G-1 Appeal Activity in the Public Assistance Programs, January 2006

Appeal Activity in the Public Assistance Programs, January 2006

G-1 Appeal Activity in the Public Assistance Programs, February 2006

Appeal Activity in the Public Assistance Programs, February 2006

G-1 Appeal Activity in the Public Assistance Programs, March 2006

G-1 - March 2006 - Appeal Activity in the Public Assistance Programs

Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

Carte de la Grèce ancienne pour servir à l'histoire des Juifs de Mr. Prideaux / G. par L. Borde

Échelle(s) : [1:2 900 000 environ], Echelle, Stades grecs a 600 au D. [600 = 3,8 cm]