Vitamin D Binding Protein Genotype and Osteoporosis

Osteoporosis is a bone disease leading to an increased fracture risk. It is considered a complex multifactorial genetic disorder with interaction of environmental and genetic factors. As a candidate gene for osteoporosis, we studied vitamin D binding protein (DBP, or group-specific component, Gc), which binds to and transports vitamin D to target tissues to maintain calcium homeostasis through the vitamin D endocrine system. DBP can also be converted to DBP-macrophage activating factor (DBP-MAF), which mediates bone resorption by directly activating osteoclasts. We summarized the genetic linkage structure of the DBP gene. We genotyped two single-nucleotide polymorphisms (SNPs, rs7041 = Glu416Asp and rs4588 = Thr420Lys) in 6,181 elderly Caucasians and investigated interactions of the DBP genotype with vitamin D receptor (VDR) genotype and dietary calcium intake in relation to fracture risk. Haplotypes of the DBP SNPs correspond to protein variations referred to as Gc1s (haplotype 1), Gc2 (haplotype 2), and Gc1f (haplotype3). In a subgroup of 1,312 subjects, DBP genotype was found to be associated with increased and decreased serum 25-(OH)D3 for haplotype 1 (P = 3 × 10−4) and haplotype 2 (P = 3 × 10−6), respectively. Similar associations were observed for 1,25-(OH)2D3. The DBP genotype was not significantly associated with fracture risk in the entire study population. Yet, we observed interaction between DBP and VDR haplotypes in determining fracture risk. In the DBP haplotype 1-carrier group, subjects of homozygous VDR block 5-haplotype 1 had 33% increased fracture risk compared to noncarriers (P = 0.005). In a subgroup with dietary calcium intake <1.09 g/day, the hazard ratio (95% confidence interval) for fracture risk of DBP hap1-homozygote versus noncarrier was 1.47 (1.06–2.05). All associations were independent of age and gender. Our study demonstrated that the genetic effect of the DBP gene on fracture risk appears only in combination with other genetic and environmental risk factors for bone metabolism

Specific treatment of problems of the spine (STOPS): design of a randomised controlled trial comparing specific physiotherapy versus advice for people with subacute low back disorders

<p>Abstract</p> <p>Background</p> <p>Low back disorders are a common and costly cause of pain and activity limitation in adults. Few treatment options have demonstrated clinically meaningful benefits apart from advice which is recommended in all international guidelines. Clinical heterogeneity of participants in clinical trials is hypothesised as reducing the likelihood of demonstrating treatment effects, and sampling of more homogenous subgroups is recommended. We propose five subgroups that allow the delivery of specific physiotherapy treatment targeting the pathoanatomical, neurophysiological and psychosocial components of low back disorders. The aim of this article is to describe the methodology of a randomised controlled trial comparing specific physiotherapy treatment to advice for people classified into five subacute low back disorder subgroups.</p> <p>Methods/Design</p> <p>A multi-centre parallel group randomised controlled trial is proposed. A minimum of 250 participants with subacute (6 weeks to 6 months) low back pain and/or referred leg pain will be classified into one of five subgroups and then randomly allocated to receive either physiotherapy advice (2 sessions over 10 weeks) or specific physiotherapy treatment (10 sessions over 10 weeks) tailored according to the subgroup of the participant. Outcomes will be assessed at 5 weeks, 10 weeks, 6 months and 12 months following randomisation. Primary outcomes will be activity limitation measured with a modified Oswestry Disability Index as well as leg and back pain intensity measured on separate 0-10 Numerical Rating Scales. Secondary outcomes will include a 7-point global rating of change scale, satisfaction with physiotherapy treatment, satisfaction with treatment results, the Sciatica Frequency and Bothersomeness Scale, quality of life (EuroQol-5D), interference with work, and psychosocial risk factors (Orebro Musculoskeletal Pain Questionnaire). Adverse events and co-interventions will also be measured. Data will be analysed according to intention to treat principles, using linear mixed models for continuous outcomes, Mann Whitney U tests for ordinal outcomes, and Chi-square, risk ratios and risk differences for dichotomous outcomes.</p> <p>Discussion</p> <p>This trial will determine the difference in outcomes between specific physiotherapy treatment tailored to each of the five subgroups versus advice which is recommended in guidelines as a suitable treatment for most people with a low back disorder.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12609000834257.aspx">ACTRN12609000834257</a>.</p

Recent invasion by a non-native cyprinid (common bream Abramis brama) is followed by major changes in the ecological quality of a shallow lake in southern Europe

We present an example of how an invasion by a non-native cyprinid (common bream, Abramis brama (Pisces: Cyprinidae), hereafter bream) in a natural shallow lake in southern Europe (Lake Montorfano, northern Italy) may have adversely affected the state of the lake’s ecosystem. In less than two decades, bream became the most abundant species and characterized by a stunted population with asymptotic length 33.5 cm, an estimated mean length at first maturity of 19.6 cm, a total mortality rate of 0.64 year−1 and a diet overwhelmingly dominated by microcrustaceans. Following bream establishment, nutrients and phytoplankton biomass rose, the proportion of Cyanobacteria by numbers increased markedly and water transparency decreased. Total zooplankton abundance increased with a marked increase in small cladocerans and copepods, whereas the abundance of large herbivorous cladocerans did not change. The coverage of submerged macrophytes declined, as did the abundance of native pelagic zooplanktivorous fish. The composition of the fish community shifted towards a higher proportion of zoobenthivorous species, such as bream and pumpkinseed (Lepomis gibbosus). Our results indicate that bream affected water quality through bottom-up mechanisms, while top-down effects were comparatively weak. Selective removal of bream and perhaps stocking of native piscivores might improve the ecological status of the lake

The DBP Phenotype Gc-1f/Gc-1f Is Associated with Reduced Risk of Cancer. The Tromsø Study.

In addition to its role as a transport protein, the vitamin D binding protein (DBP) may also affect lipid metabolism, inflammation and carcinogenesis. There are three common variants of the DBP, Gc1s (1s), Gc1f (1f), Gc2 (2) that result in six common phenotypes (1s/1s, 1s/1f, 1s/2, 1f/1f, 1f/2, and 2/2). These phenotypes can be identified by genotyping for the two single nucleotide polymorphisms rs7041 and rs4588 in the GC gene. The DBP variants have different binding coefficients for the vitamin D metabolites, and accordingly there may be important relations between DBP phenotypes and health.DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints myocardial infarction (MI), type 2 diabetes (T2DM), cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2010- 2013. Genotyping was performed for rs7041 and rs4588 and serum 25-hydroxyvitamin D (25(OH)D) was measured.Genotyping for rs7041 and rs4588 was performed successfully in 11 704 subjects. Among these, 1660 were registered with incident MI, 958 with T2DM, 2410 with cancer and 4318 had died. Subjects with the DBP phenotype 1f/1f had 23 - 26 % reduced risk of incident cancer compared to the 1s/1s and 2/2 phenotypes (P < 0.02, Cox regression with gender as covariate). Differences in serum 25(OH)D levels could not explain the apparent cancer protective effect of the DBP variant 1f. In addition to cancer and 25(OH)D, there were significant associations between DBP phenotype and body height, hip circumference and serum calcium.There are important biological differences between the common DBP phenotypes. If the relation between the DBP variant 1f and cancer is confirmed in other studies, determination of DBP phenotype may have clinical importance