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This study was designed to evaluate both the frequency and the course of impairments, disabilities, and handicaps resulting from trauma. It was conducted in Aquitaine, France, on a sample of 1005 trauma patients (mean ISS, 10.5 +/- 0.3) in which severe trauma (ISS > 25) was rather overrepresented (169 of 1005). A prospective follow-up of disablement according to the WHO classification was based on medical examinations performed 6 and 12 months after the trauma. Of 664 survivors reviewed at 6 months, the findings were cross tabulated with Injury Severity Score (ISS) and age. There was a good relationship between ISS and the mean length of stay in the hospital (r = 0.46; p < 0.001), the duration of rehabilitation, and the time away from work or school. Out of this sample of 1005 patients with rather major injuries, 73% of the survivors suffered from at least one impairment, with a consistently lower frequency in children whatever the severity. At least one disability was encountered in 52.3% of these patients depending on both ISS and age. Handicap was noted in at least 26% of the cases. Between the sixth month and the end of the first year, the minimal handicap regression was 35.8%, whereas the minimal regression of the disability rate was 19.5%. The best improvement was observed essentially in the low ISS categories. Whereas for minor trauma the course of disablement seems to be fixed 1 year after the injury, such is not the case for severe trauma.

Human secreted phospholipases A2 (sPLA2s) represent novel attractive therapeutic targets and biomarkers in coronary artery diseases (CAD). We have shown that human Group X sPLA2 (hGX sPLA2) is present in atherosclerotic lesions and that hGX sPLA2 modified LDL induces foam cell formation. To elucidate whether hGX sPLA2 has a causative role in CAD we have screened the human PLA2G10 gene to identify frequent polymorphisms, and we have examined their possible association with cardiovascular end-points and intermediate inflammatory phenotypes in a large prospective study of patients with CAD (the AtheroGene study). Although no significant association was found between the various polymorphisms identified and lipids or inflammatory markers, patients carriers of the C allele of the T-512C polymorphism located in the 5’ untranslated region showed a decreased risk of recurrent cardiovascular events. Molecular analysis of the only missense variant (R38C) showed its functional relevance as it leads to a profound change in expression and secretion of hGX sPLA2.

In a European study an insertion (/)/deletion (D) polymorphism in the angiotensin converting enzyme (ACE) gene has been shown to be associated with the risk of myocardial infarction (Ml). In the same study, we investigated the association of the polymorphism with a parental history of fatal MI. There was an excess of both DD (odds ratio 2·6, p=0·02) and ID (odds ratio=1·9, p=0·08) genotypes among those having a parental history of Ml, confirming that genetic variation in the ACE locus could be involved in the risk of MI.

Inter-individual variability in telomere length is highly heritable and has been correlated with risk of coronary heart disease (CHD). Our aim was to determine the association of mean leukocyte telomere length with paternal history of premature myocardial infarction (MI). Mean leukocyte telomere length was measured with real-time polymerase chain reactions in 369 male students (18–28 years) with a paternal history of MI before the age of 55, recruited from 14 European universities, serving as cases and 396 age-matched controls with no paternal history of CHD. Overall, cases had borderline significantly shorter mean length (~550 bp), adjusted for age and geographical region, than controls (p = 0.05). A significant difference in telomere length across the geographical regions of Europe was observed (p

The aim of this study was to investigate the influence of APOA5 variants on fasting lipids and to the response to both an oral fat tolerance test (OFTT) and an oral glucose tolerance test (OGTT). The association of two APOA5 SNPs [S19W (SNP5), −1131T>C (SNP3)] and an APOA4/A5 intergenic SNP [−12238T>C (SNP4)] were examined in healthy young men (n=774) who had undergone both an OFTT and an OGTT. Both −1131T>C and S19W rare alleles were associated with triglyceride (TG)-raising effects (11%, P=0.008; 21% (in cases), PC rare allele was associated with higher waist to hip ratio (P

Background Variations at the DNA level with moderate effects on biochemical variables may be important for the occurrence of disease at the population level, if they are common. Two mutations in the LPL gene, N9 and S291, are associated with variation in fasting plasma concentrations of HDL cholesterol (HDL-C) and triglycerides (TG). We investigated whether these mutants were more frequent in offspring of cases with premature coronary disease and analyzed the effects on fasting plasma lipids and postprandial TG. Methods and Results Students with and without paternal history of myocardial infarction (cases and control subjects [controls]) were studied in the European Atherosclerosis Research Studies I and II (EARS-I and -II). Allelic frequencies for the N9 and S291 mutations did not differ between cases and control subjects. The N9 mutation was identified in 4.2% of all subjects in EARS-I, and carriers had higher fasting TG levels ( P P P P Conclusions The two LPL mutations are common and may predispose to elevated TG and decreased HDL-C concentrations, even in young subjects. In the case of the S291 mutation, this effect appears to be mediated via delayed postprandial TG clearance. Moreover, even moderate obesity potentiates the TG-raising and HDL-lowering effects associated with the S291 allele.

Background 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 IL18 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, IL18R1 and IL18RAP, with the risk of developing CVD. Methods Eleven tagging SNPs, 5 in IL18R1 and 6 in IL18RAP, 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. Results 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 IL18 SNPs previously studied in the MORGAM project, and between SNPs and environmental factors remained unfruitful. Conclusion Our analysis suggests that the variability of IL18R1 and IL18RAP genes are unlikely to contribute to modulate the risk of CVD.