A large-sample assessment of possible association between ischaemic stroke and rs12188950 in the PDE4D gene.

Previous reports have shown ambiguous findings regarding the possible associations between ischaemic stroke (IS) and single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) gene region. The SNP rs12188950 (or SNP45) has often been studied in this context. We performed a multi-centre study involving a large sample of 2599 IS patients and 2093 control subjects from the south and west regions of Sweden to replicate previous studies regarding IS risk and rs12188950. Subjects from Lund Stroke Register (LSR), Malmö Diet and Cancer Study (MDC) and Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) were enroled. Subgroups of participants with hypertension and participants <55 years of age, as well as the TOAST subgroups large vessel disease, small vessel disease and cardioembolism, were also assessed. Univariate odds ratios (ORs) and ORs controlling for hypertension, diabetes and current smoking were calculated. We additionally performed a meta-analysis including 10,500 patients and 10,102 control subjects from 17 publications (including the present study). When assessing pooled data from LSR, MDC and SAHLSIS we obtained no association between IS and rs12188950 for all participants (OR=0.93; 95% confidence interval (CI): 0.83-1.05). Significant associations were not found for hypertensive participants or participants with age <55, or when separately evaluating patients from the three different TOAST subgroups. The meta-analysis showed no significant overall estimate (OR=0.96; 95% CI: 0.89-1.04) with significant heterogeneity for random effect (P=0.042). No effect from rs12188950 on IS was found from either our pooled multi-centre data or the performed meta-analysis. We did not find any association between the examined subgroups and rs12188950 either.

Genetics in clinical practice: general practitioners' educational priorities in European countries.

PURPOSE: To assess how general practitioners (GPs) from European countries prioritized their genetic educational needs according to their geographic, sociodemographic, and educational characteristics. METHODS: Cross-sectional survey, random and total samples of GPs in five European countries (France, Germany, the Netherlands, Sweden, and United Kingdom), mailed questionnaires; OUTCOME: Genetic Educational Priority Scale (30 items; six subscores). RESULTS: A total 1168 GPs answered. Priorities differed (P < 0.001) but were consistently ranked across the countries. Previous education had a marginal effect on priorities. Women gave higher priorities than men to Genetics of Common Disorders (adjusted odds ratio [OR adj], 2.5; 95% confidence interval [CI], 1.6-3.8), Psychosocial and Counseling Issues (OR adj, 1.6; 95% CI, 1.1-2.5), and Ethical, Legal, and Public Health Issues (OR adj, 1.3; 95% CI, 1.1-1.8), but lower than men to Techniques and Innovation in Genetics (OR adj, 0.7; 95% CI, 0.5-0.9). Older physicians gave higher priorities to Basic Genetics and Congenital Malformations (OR adj, 1.5; 95% CI, 1.1-1.9), and to Techniques and Innovation in Genetics (OR adj: 1.3; 95% CI, 1.0-1.7), compared with their younger colleagues. CONCLUSIONS: Expressed genetic educational needs vary according to the countries and sociodemographics. In accordance, training could be more focused on genetics of common disorders and on how to approach genetic risk in clinical practice rather than on ethics, new technologies, or basic concepts.

EuroGentest: DNA-based testing for heritable disorders in Europe.

OBJECTIVES: Regarding the recent attention to develop policies regarding the provision of clinical genetic testing services, access to, acceptance, utilisation and regulation of genetic services was investigated in selected European countries as well as one non-European country. METHODS: Data were collected on the basis of relevant international reports and sources accessible via the internet, from self- designed, internationally administered surveys and with the help of a panel of experts from European countries participating in several workshops as well as from National European Societies of Human Genetics. RESULTS: A selection of divergent health care systems was reviewed and compared (e.g. Finland, Germany, Portugal, Sweden, UK, France, Italy, Spain, Czech Republic, Lithuania and Serbia/Montenegro). For the evaluation of clinical validity and utility of genetic testing, background information was provided focussing on DNA-based testing for heritable disorders with a strong genetic component (usually due to the action of a single gene). CONCLUSIONS: There is great heterogeneity in genetic testing services among the countries surveyed. It is premature to mandate that genetic testing provided by clinical services meets professional standards regarding clinical validity and utility, because there is to date no consensus within the scientific community and among health care providers to what extent clinical validity and utility can and need to be assessed. Points to consider in the process of developing such standards are proposed.

The need for oncogenetic counselling. Ten years' experience of a regional oncogenetic clinic.

A monogenic inheritance, mainly seen as a dominant pattern, accounts for 5-10% of all cancer cases. The increased knowledge and identification of high-risk genes have led to a need for specialized cancer family clinic was the expression used by Eeles and Murday. The Oncogenetic Clinic at the University Hospital in Lund was started in 1993 and the authors' 10-year experience is summarized in this paper. The clinic offers service to the South Swedish Health Care Region comprising a total of 1.6 million inhabitants. During these first 10 years a total of 1059 individuals from 789 families have been individually counselled. The most common reason for referral was a family history of breast cancer, followed by a family history of colorectal cancer. According to the commonly used criteria, 437 (55%) of the families were considered as autosomal dominantly inherited; 147 families (19%) did not fulfil these criteria but had a strong clustering of breast/ovarian or colorectal/endometrial cancer. The remaining 205 families (26%) were not recognized as any previously described hereditary cancer syndrome with early onset. However, most of these families had a family history of cancer. Mutation analysis was performed in 386/789 (49%) of the families. In families with breast and ovarian cancer a genetic aberration was identified in 45/76 (59%) and in breast-only families in 27/129 (21%). In MSI-positive colon cancer families 16/34 (47%) of the families had a germline mutation. Thus, the majority of the families referred to the clinic were in obvious need of genetic counselling concerning cancer and heredity and in a substantial number of the families a germline mutation could be identified.