Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes.

We have previously reported suggestive linkage of type 2 diabetes mellitus to chromosome 10q. We genotyped 228 microsatellite markers in Icelandic individuals with type 2 diabetes and controls throughout a 10.5-Mb interval on 10q. A microsatellite, DG10S478, within intron 3 of the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4) was associated with type 2 diabetes (P = 2.1 x 10(-9)). This was replicated in a Danish cohort (P = 4.8 x 10(-3)) and in a US cohort (P = 3.3 x 10(-9)). Compared with non-carriers, heterozygous and homozygous carriers of the at-risk alleles (38% and 7% of the population, respectively) have relative risks of 1.45 and 2.41. This corresponds to a population attributable risk of 21%. The TCF7L2 gene product is a high mobility group box-containing transcription factor previously implicated in blood glucose homeostasis. It is thought to act through regulation of proglucagon gene expression in enteroendocrine cells via the Wnt signaling pathway.

The gene encoding phosphodiesterase 4D confers risk of ischemic stroke.

We previously mapped susceptibility to stroke to chromosome 5q12. Here we finely mapped this locus and tested it for association with stroke. We found the strongest association in the gene encoding phosphodiesterase 4D (PDE4D), especially for carotid and cardiogenic stroke, the forms of stroke related to atherosclerosis. Notably, we found that haplotypes can be classified into three distinct groups: wild-type, at-risk and protective. We also observed a substantial disregulation of multiple PDE4D isoforms in affected individuals. We propose that PDE4D is involved in the pathogenesis of stroke, possibly through atherosclerosis, which is the primary pathological process underlying ischemic stroke.

Identification of type VI secretion systems in Moritella viscosa.

The study describes the identification of type VI secretion systems (T6SSs) in Moritella viscosa, the aetiological agent of winter ulcer disease. Despite the availability of commercial vaccines, M. viscosa causes significant financial losses in salmonid farming. The T6SS transports bacterial proteins from the cell into the environment or directly into host cells, and has been implicated with bacterial virulence. The aim of the study was to identify potential T6SSs in M. viscosa and to determine whether it possesses active T6S, providing further insight into the biology of the bacterium. The genome of M. viscosa 06/09/139 was screened for homology with known T6SS encoding genes. Two genetically distinct loci, termed Moritella Type Six Secretion 1 and 2 (mts1 and mts2), were identified as encoding putative T6SSs. Each locus contained known T6S core genes. The mts2 locus contained species specific genes, some of which have not previously been connected with T6S. The mts1 locus showed sequence homology and synteny to T6SSs of the fish pathogen Aliivibrio salmonicida and a non-pathogenic Moritella sp. PE36. The mts2 locus was more similar to a Vibrio parahaemolyticus T6SS. A functional T6SS was confirmed through identification of secreted Mts1-M, a hemolysin coregulated protein (Hcp) which is a part of the secretion system. Both virulent and avirulent M. viscosa isolates expressed two genes encoding Hcp, mts1-M and mts2-M. The results show that M. viscosa has a functional T6S, but the role of the secretion system and possible connections with virulence need further examination.

[Quality indicators of drug therapy at hospital admission among elderly patients]. / Vísbendingar um gædi lyfjamedferda aldradra vid innlögn á landspítala.

OBJECTIVE: Increased morbidity and higher prevalence of medication use commonly coexists among the elderly. When managed appropriately, older patients can benefit from drug therapy. However, drug related problems are more frequent and more serious in the elderly. The aim of the study was to assess the quality of medication use in older people at hospital admission. MATERIAL AND METHODS: A retrospective medical record review was performed for patients 70 years and older who had an unplanned admission to the internal medicine and geriatric units at Landspitali University Hospital in 2007. Among the sampled medical records, 913 met inclusion criteria. Assessment was carried out using 15 drug-specific quality indicators. RESULTS: Mean age was 80.9 years and 54.5% were women. Mean number of drugs at admission was 7.0 for women and 6.5 for men (p=0.047). The prevalence of having one or more quality indicators on admission was 48.4%. Women were more likely to have a quality indicator than men (women 56.2%, men 39.9%). The probability also increased with increasing age and number of drugs. CONCLUSIONS: The quality of drug therapy among older patients at hospital admission appears to be suboptimal. A more accurate estimate of the problem could be obtained through a prospective study where drug regimens are correlated with symptoms and reason for admission. Additional studies are also needed in the outpatient setting. Such studies could provide more accurate evidence and assist policy making towards improved quality of drug prescribing for a growing number of older patients. KEYWORDS: elderly, quality indicators, hospitalization, drugs, inappropriate prescribing.

Localization of a susceptibility gene for common forms of stroke to 5q12.

Stroke is one of the most complex diseases, with several subtypes, as well as secondary risk factors, such as hypertension, hyperlipidemia, and diabetes, which, in turn, have genetic and environmental risk factors of their own. Here, we report the results of a genomewide search for susceptibility genes for the common forms of stroke. We cross-matched a population-based list of patients with stroke in Iceland with an extensive computerized genealogy database clustering 476 patients with stroke within 179 extended pedigrees. Linkage to 5q12 was detected, and the LOD score at this locus meets the criteria for genomewide significance (multipoint allele-sharing LOD score of 4.40, P=3.9 x 10(-6)). A 20-cM region on 5q was physically and genetically mapped to obtain accurate marker order and intermarker distances. This locus on 5q12, which we have designated as "STRK1," does not correspond to known susceptibility loci for stroke or for its risk factors and represents the first mapping of a locus for common stroke.