Genetic association analyses reveal a role for vitamin D insufficiency in hepatitis C virus-associated hepatocellular carcinoma development

Background: V itamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. Methods: Associations between t he r isk o f HCV-related HCC development and CYP2R1 , GC, and DHCR7 genotypes, which are genetic determinants of reduced 25-OH-vitamin D3 (25[OH]D3) serum levels, were determined. Results: A t otal of 5604 HCV-infected patients, 1279 with a nd 4325 without progression to HCC, w ere identified. The well-known association between 25(OH)D3 s erum levels and variations in CYP2R1 ( rs1993116, rs10741657), GC ( rs2282679), a nd DHCR7 ( rs7944926, rs12785878) g enotypes was also apparent in patients w ith chronic hepatitis C. The same genotypes of t hese single nucleotide polymorphisms (SNPs), w hich are associated with reduced 25(OH)D3 s erum levels, were significantly associated with HCV-associated HCC (P=0.07 [OR=1.13] for CYP2R1 , P=0.007 [OR=1.56] for GC, P=0.003 [OR=1.42] for DHCR7; ORs for risk genotypes). In contrast, no association between t hese genetic variations and the o utcome of antiviral therapy with pegylated interferon-α and ribavirin ( P>0.2 for e ach SNP) or liver fibrosis progression rate (P>0.2 for each SNP) was observed, s uggesting a specific influence o f the genetic d eterminants of 25(OH)D3 s erum levels o n hepatocarcinogenesis. Conclusions: Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related HCC development. Controlled clinical trials to assess the benefit of vitamin D supplementation in HCVinfected patients with advanced liver fibrosis or cirrhosis are warranted.

Colombes, 25/4/20, [football] association, armée anglaise contre armée française : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59045

Colombes, 25/4/20, [football] association, équipe [de l']armée française : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59051

Colombes, 25/4/20, [football] association, équipe [de l']armée française : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59052

Colombes, 25/4/20, [football] association, équipe [de l']armée anglaise : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59053

Colombes, 25/4/20, [football] association, équipe [de l']armée anglaise : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59054

5-4-20, Saint-Ouen, [football] association, équipe du Leytonstone F.C. de Londres : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58743

Association of MMP-2 polymorphisms with severe and very severe COPD: a case control study of MMPs-1, 9 and 12 in a European population.

BACKGROUND: Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis of the pathogenesis of COPD. These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease--antiprotease imbalance theory for the cause of COPD. Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies. METHODS: To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations. We used logistic regression to adjust for age, gender, centre and smoking history. RESULTS: Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV. CONCLUSIONS: Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94). The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129). This implicates haplotypes of MMP-12 as modifiers of disease severity.

Revue des études grecques : publication trimestrielle de l'Association pour l'encouragement des études grecques / Théodore Reinard, rédacteur en chef

1888/07 (T1,N3)-1888/09.

Revue des études grecques : publication trimestrielle de l'Association pour l'encouragement des études grecques / Théodore Reinard, rédacteur en chef

1891/10 (T4,N16)-1891/12.

Revue des études grecques : publication trimestrielle de l'Association pour l'encouragement des études grecques / Théodore Reinard, rédacteur en chef

1904/07 (T17,N76)-1904/10 (T17,N77).