Fine mapping the CETP region reveals a common intronic insertion associated to HDL-C

Background: Individuals with exceptional longevity and their offspring have significantly larger high-density lipoprotein concentrations (HDL-C) particle sizes due to the increased homozygosity for the I405V variant in the cholesteryl ester transfer protein (CETP) gene. In this study, we investigate the association of CETP and HDL-C further to identify novel, independent CETP variants associated with HDL-C in humans. Methods: We performed a meta-analysis of HDL-C within the CETP region using 59,432 individuals imputed with 1000 Genomes data. We performed replication in an independent sample of 47,866 individuals and validation was done by Sanger sequencing. Results: The meta-analysis of HDL-C within the CETP region identified five independent variants, including an exonic variant and a common intronic insertion. We replicated these 5 variants significantly in an independent sample of 47,866 individuals. Sanger sequencing of the insertion within a single family confirmed segregation of this variant. The strongest reported association between HDL-C and CETP variants, was rs3764261; however, after conditioning on the five novel variants we identified the support for rs3764261 was highly reduced (βunadjusted=3.179 mg/dl (P value=5.25×10−509), βadjusted=0.859 mg/dl (P value=9.51×10−25)), and this finding suggests that these five novel variants may partly explain the association of CETP with HDL-C. Indeed, three of the five novel variants (rs34065661, rs5817082, rs7499892) are independent of rs3764261. Conclusions: The causal variants in CETP that account for the association with HDL-C remain unknown. We used studies imputed to the 1000 Genomes reference panel for fine mapping of the CETP region. We identified and validated five variants within this region that may partly account for the association of the known variant (rs3764261), as well as other sources of genetic contribution to HDL-C

A nursing service change strategy for health clinics

M.Cur.It is evident that the current political changes presently taking place in South Africa need to be accompanied by a dramatic transformation to accommodate the economic, social, technological and health changes amongst others. The nursing discipline is no exception. For a change to be felt by nursing staff and by health consumers, effective management strategies need to be developed to accommodate transformation guidelines as outlined by the Reconstruction and Development Programme, the National Health Plan and the Constitution which all emphasize the right to health, hence this study. This study focuses on a primary health care clinics. This is a qualitative, contextual, exploratory and descriptive study with the overall aim of exploring and describing a nursing service strategy for change in Soweto Primary Health clinics where the researcher is employed. To accomplish this aim, the following objectives were formulated: to explore and describe the expectations of the managers and the functional nurses concerning the required nursing service strategy for change within Soweto Primary Health Clinics; to explore and describe the expectations of health consumers concerning the required nursing service strategy for change in Soweto Primary Health Clinics; to describe the required nursing service strategy for Soweto Primary Health Clinics. Through purposive sampling, three focus groups were selected from the role players within Soweto who represent the nursing managers, the functional nurses' and the health consumers in order to infer the required change strategy for the nursing service. i. Data was collected through these focus groups interviews using semi-structured questions. Data management and data analysis was done using the methods of content analysis according to Kerlinger (1986: 480). An research expert, was utilised as a reliability measure to identify and categorise themes separately from the researcher. The categories that emerged were subsequently refined through consensus discussions between the researcher and the independent researcher. Woods and Catanzaro' s measures (1988: 136) to ensure validity and reliability were applied in this study

Fine mapping the CETP region reveals a common intronic insertion associated to HDL-C

BACKGROUND: Individuals with exceptional longevity and their offspring have significantly larger high-density lipoprotein concentrations (HDL-C) particle sizes due to the increased homozygosity for the I405V variant in the cholesteryl ester transfer protein (CETP) gene. In this study, we investigate the association of CETP and HDL-C further to identify novel, independent CETP variants associated with HDL-C in humans. METHODS: We performed a meta-analysis of HDL-C within the CETP region using 59,432 individuals imputed with 1000 Genomes data. We performed replication in an independent sample of 47,866 individuals and validation was done by Sanger sequencing. RESULTS: The meta-analysis of HDL-C within the CETP region identified five independent variants, including an exonic variant and a common intronic insertion. We replicated these 5 variants significantly in an independent sample of 47,866 individuals. Sanger sequencing of the insertion within a single family confirmed segregation of this variant. The strongest reported association between HDL-C and CETP variants, was rs3764261; however, after conditioning on the five novel variants we identified the support for rs3764261 was highly reduced (βunadjusted=3.179 mg/dl (P value=5.25×10-509), βadjusted=0.859 mg/dl (P value=9.51×10-25)), and this finding suggests that these five novel variants may partly explain the association of CETP with HDL-C. Indeed, three of the five novel variants (rs34065661, rs5817082, rs7499892) are independent of rs3764261. CONCLUSIONS: The causal variants in CETP that account for the association with HDL-C remain unknown. We used studies imputed to the 1000 Genomes reference panel for fine mapping of the CETP region. We identified and validated five variants within this region that may partly account for the association of the known variant (rs3764261), as well as other sources of genetic contribution to HDL-C