Lack of association between polymorphisms of the IL18R1 and IL18RAP genes and cardiovascular risk: the MORGAM Project

<p>Abstract</p> <p>Background</p> <p>Interleukin-18 is a pro-inflammatory cytokine suspected to be associated with atherosclerosis and its complications. We had previously shown that one single nucleotide polymorphism (SNP) of the <it>IL18 </it>gene was associated with cardiovascular disease (CVD) through an interaction with smoking. As a further step for elucidating the contribution of the IL-18 pathway to the etiology of CVD, we here investigated the association between the genetic variability of two IL-18 receptor genes, <it>IL18R1 </it>and <it>IL18RAP</it>, with the risk of developing CVD.</p> <p>Methods</p> <p>Eleven tagging SNPs, 5 in <it>IL18R1 </it>and 6 in <it>IL18RAP</it>, characterizing the haplotypic variability of the corresponding genes; were genotyped in 5 European prospective CVD cohorts including 1416 cases and 1772 non-cases, as part of the MORGAM project. Both single-locus and haplotypes analyses were carried out to investigate the association of these SNPs with CVD.</p> <p>Results</p> <p>We did not find any significant differences in allele, genotype and haplotype frequencies between cases and non-cases for either of the two genes. Moreover, the search for interactions between SNPs located in different genes, including 5 <it>IL18 </it>SNPs previously studied in the MORGAM project, and between SNPs and environmental factors remained unfruitful.</p> <p>Conclusion</p> <p>Our analysis suggests that the variability of <it>IL18R1 </it>and <it>IL18RAP </it>genes are unlikely to contribute to modulate the risk of CVD.</p

Méthodologie statistique pour l'analyse de polymorphismes génétiques dans une étude de type cas-cohorte (application au projet MORGAME)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

Rates of immunization against pandemic and seasonal influenza in persons at high risk of severe influenza illness: a cross-sectional study among patients of the French Sentinelles general practitioners.

International audienceBACKGROUND: Three main categories of persons are targeted by the French influenza vaccination strategy: all persons aged 65 years or over, those aged less than 65 years with certain underlying medical conditions and health care workers. The main objective of this study was to estimate rates of influenza immunization in these target groups attending a medical consultation for two consecutive influenza seasons: 2009--2010 (seasonal and pandemic vaccines) and 2010--2011 (seasonal vaccine). METHODS: A standardized questionnaire was mailed to 1323 general practitioners (GPs) of the Sentinelles Network, collecting data on all patients seen on a randomly assigned day. For every patient, following information was collected: age, gender, BMI, presence of any medical condition that increases risk of severe influenza illness, and vaccination status for the three vaccines mentioned. RESULTS: Two hundred and three GPs agreed to participate and included 4248 patients. Overall, in persons with high risk of severe influenza, the estimated vaccine coverages (VC) were 60%, (95% CI = 57%; 62%) for the seasonal vaccine in 2010--2011, 61% (59%; 63%) for the seasonal vaccine in 2009--2010 and 23% (21%; 25%), for the pandemic vaccine in 2009--2010. Among people aged 65 years and over (N=1259, 30%) VC was estimated for seasonal vaccines at 72% (70%; 75%) in 2010--2011 and 73% (71%; 76%) in 2009--2010, and 24% (22%; 26%) for the pandemic vaccine. The lowest seasonal VC were observed in younger persons (<65 years) with underlying medical conditions, in particular pregnant women (<10%) and overweight persons (<30%). CONCLUSIONS: Our study shows that influenza vaccination coverage among patients of the French Sentinelles general practitioners remains largely below the target of 75% defined by the 2004 French Public Health Law, and underscores the need for the implementation of public health interventions likely to increase vaccination uptake

Association between miR-31-3p expression and cetuximab efficacy in patients with KRAS wild-type metastatic colorectal cancer: a post-hoc analysis of the New EPOC trial

BACKGROUND: High miR-31-3p expression is associated with inferior outcomes in KRAS wild-type (WT) advanced colorectal cancer patients treated with anti- EGFR therapy. This study evaluated miR-31-3p expression in patients with operable colorectal liver metastases (LM) enrolled in the New EPOC study. METHODS: MiR-31-3p expression was measured in primary tumors (PT) from 149 KRAS WT patients including 71 receiving chemotherapy alone (CT) and 78 receiving chemotherapy plus cetuximab (CTX). Each treatment arm was split into tertiles based on miR-31-3p expression levels. MiR-31-3p expression was also measured in LM from 94 patients with tumor tissue available. RESULTS: The median progression-free survival for the combined populations with mid or high miR-31-3p expression was shorter in the CTX versus the CT arm (26.7 months versus 12.3 months, HR=2.28 95%CI 1.27; 4.09 p=0.006). Low miR-31-3p expressers had similar outcomes irrespective of treatment (HR=1.06 95%CI 0.43; 2.61 p=0.9). MiR-31-3p expression was correlated between paired PT and LM samples in the CT group but not in the CTX group. CONCLUSIONS: Patients with low miR-31-3p expression in the New EPOC study were not harmed by the addition of cetuximab. This supports miR-31-3p as a promising predictive biomarker for anti-EGFR therapy in KRAS WT advanced colorectal cancer