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Baumert J.,Helmholtz Center for Environmental Research | Huang J.,Lung and Blood Institutes Framingham Heart Study | Huang J.,U.S. National Institutes of Health | Huang J.,Wellcome Trust Sanger Institute | And 129 more authors.
PLoS ONE | Year: 2014

Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2×10-8. This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations. © 2014 Baumert et al.

PubMed | Folkhalsan Research CentreHelsinki and University of Turku
Type: Journal Article | Journal: European journal of endocrinology | Year: 2016

Non-pharmacological interventions are important in reducing risk for osteoporotic fractures. We investigated the effects of a 16-week individualized resistance training intervention on bone mineral density (BMD), bone turnover markers and 10-year relative risk (RR) for osteoporotic fracture.Interventional study with a follow-up.In total, 37 elderly women (mean age 71.9 3.1 years) with decreased muscle strength participated in the resistance training intervention three times per week with 60 min per session for 16 weeks under the supervision of a licensed physiotherapist. Total hip BMD with quantitative CT, bone markers (sclerostin, osteocalcin, CTX, PINP, IGF-1, 25(OH)-D) and 10-year RR for osteoporotic fracture were measured at baseline, post-intervention and at 1-year follow-up after the end of the intervention. Eleven age- and sex-matched controls did not participate in the intervention but were studied at baseline and at 1-year follow-up.Resistance training seemed to increase total hip BMD by 6% (P = 0.005). Sclerostin (P < 0.001) and total osteocalcin (P = 0.04) increased while other bone markers remained unchanged. A 10-year RR for major osteoporotic and hip fracture remained unchanged. At follow-up total hip BMD (P < 0.001) decreased back to the baseline level with a simultaneous decrease in serum sclerostin (P = 0.045), CTX (P < 0.001) and an increase in 25(OH)-D (P < 0.001), 10-year RR for major osteoporotic (P = 0.002) and hip fracture (P = 0.01).Our findings suggest an important role of continuous supervised resistance training for the prevention of osteoporotic fractures in elderly women with decreased muscle strength.

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