Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.

The diversity of microorganisms present in a sediment colonized by the phanerogam Zostera noltii has been analyzed. Microbial DNA was extracted and used for constructing two 16S rDNA clone libraries for Bacteria and Archaea. Bacterial diversity was very high in these samples, since 57 different sequences were found among the 60 clones analyzed. Eight major lineages of the Domain Bacteria were represented in the library. The most frequently retrieved bacterial group (36% of the clones) was ␦-Proteobacteria related to sulfate-reducing bacteria. The second most abundant group (27%) was ␥-Proteobacteria, including five clones closely related to S-oxidizing endosymbionts. The archaeal clone library included members of Crenarchaeota and Euryarchaeota, with nine different sequences among the 15 analyzed clones, indicating less diversity when compared to the Bacteria organisms. None of these sequences was closely related to cultured Archaea organisms.Our objective in this study was to describe the diversity of the prokaryotic community inhabiting a marine sediment colonized by the marine phanerogam Zostera noltii located in the Bassin d'Arcachon, South-West France. This is a macrotidal coastal lagoon that represents the most extensive intertidal meadows of this rooted phanerogam in Western Europe (70 km 2 ). This seagrass ecosystem is characterized by a high iron content, 111.5 (dry weight) g/g (32) in the sediment, as well as strong tidal activity, which ensures regular mixing of the water body and exposes the sediment surface to the air for between 4 and 8 h each day. This environment is different from those that have previously been studied by molecular methods due to the presence of Z. noltii roots and rhizomes. A number of recent studies have shown that living seagrasses release dissolved organic carbon, which can significantly influence the composition and activity of the seagrass rhizosphere microflora (24, 36). For example, several studies have demonstrated high rates of heterotrophic nitrogen fixation in the rhizosphere of Z. noltii-colonized sediments which are coupled to the photosynthetic activity of the plants via the release of fixed carbon from the roots (20,24,36). Similarly, substantial stimulation of sulfate reduction rates in seagrass-colonized sediments in the light have been reported (4,25). These data indicate a close interaction between the plants and the microbial community in the rhizosphere.Samples. Z. noltii-colonized sediment cores (5-cm diameter) were collected from Station A in the Bassin d'Arcachon in July 1996 and kept in the dark at Ϫ20°C until processed. Station A is located in the center of the Bay, in an open zone subjected to marine influences. Sediment cores that contained extensive rhizome material were sliced into sections (1-cm thick, from the surface), and horizon 2 (1 to 2 cm) was chosen for the microbial community analysis.DNA extraction and purification. A combination of the methods described by Zhou et al. (37) and Gray and Herwig (14) was used. Eight hundred milligrams of ...

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