PLoS medicine
-
Multicenter Study
Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study.
Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been no very-large-scale studies of COLIA1 alleles in relation to these phenotypes. ⋯ Allowing for the inevitable heterogeneity between participating teams, this study-which to our knowledge is the largest ever performed in the field of osteoporosis genetics for a single gene-demonstrates that the COLIA1 Sp1 polymorphism is associated with reduced BMD and could predispose to incident vertebral fractures in women, independent of BMD. The associations we observed were modest however, demonstrating the importance of conducting studies that are adequately powered to detect and quantify the effects of common genetic variants on complex diseases.
-
Maggini and colleagues examine the evidence on cholinesterase inhibitors for treating dementia. "What seemed a biologically plausible intervention," they say, "has not led to a proven, real improvement in patients' well-being."
-
Meta Analysis
Five glutathione s-transferase gene variants in 23,452 cases of lung cancer and 30,397 controls: meta-analysis of 130 studies.
Glutathione S-transferases (GSTs) are known to abolish or reduce the activities of intracellular enzymes that help detoxify environmental carcinogens, such as those found in tobacco smoke. It has been suggested that polymorphisms in the GST genes are risk factors for lung cancer, but a large number of studies have reported apparently conflicting results. ⋯ The risk of lung cancer is not strongly associated with the I105V and A114V polymorphisms in the GSTP1 gene or with GSTM3 intron 6 polymorphism. Given the non-significant associations in the larger studies, the relevance of the weakly positive overall associations with the GSTM1 null and the GSTT1 null polymorphisms is uncertain. As lung cancer has important environmental causes, understanding any genetic contribution to it in general populations will require the conduct of particularly large and comprehensive studies.
-
Healy analyzes the surge in diagnoses of bipolar disorder and the evidence on the effectiveness of antipsychotic drugs and anticonvulsants in prophylaxis against the disorder.