P3-0298 — Annual report 2012
1.
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk.We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 1 17 genome-wide association studies and 32,961 1 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 1 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P ( 5 Ž 1 10Ž8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P ( 5 Ž 1 10Ž4, Bonferroni corrected), of which six reached P ( 5 Ž 1 10Ž8, including at 1 18p1111.21 (FAM210A), 7q21.3 (SLC25A13), 11 11 11q13.2 (LRP5), 4q22.1 1 (MEPE), 2p16.2 (SPTBN1) and 1 10q21.1 1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

COBISS.SI-ID: 3233137
2.
BMD values and GSTM3 gene polymorphisms in combination with GSTT1/GSTM1 genes: a genetic association study in Slovenian elderly

Background: Much research suggests that oxidative stress is associated with osteoporosis development. Glutathione S-transferases mu3 (GSTM3) are an important group of detoxifying enzymes that eliminate oxidative stress-relatedproducts. Objectives: To examine the associations of functional GSTM3 gene polymorphisms (Val224Ile and insdelAGG), their haplotypes and, in combination with GSTT1- null and GSTM1-null polymorphisms, with bone mineral density (BMD) measured at femoral neck (_fn), lumbar spine (_ls) and total hip(_th) and biochemical bone turnover markers in 593 Slovenian elderly women and 119 Slovenian elderly men. Methods: GSTM3, GSTT1-null and GSTM1-null gene polymorphisms using sizing denaturing high-performance liquid chromatography, triplex PCR method or realtime PCR; BMD_fn, BMD_ls, BMD_th values using dual energy X-ray absorptiometry, and plasma osteocalcin, serum bone alkaline phosphatase and free soluble tumor necrosis factor (ligand) superfamily, member 11 (sRANKL) concentrations using a solid-phase, two-site chemiluminescent enzyme- labeled immunometric assay, radioimmunoassay or enzyme immunoassay were determined. Statistical analysis was performed using one-way and two-way ANCOVA with adjustment for potential confounders (age, height and weight). Results: The (borderline) significant differences in BMD_th and BMD_fn values between genotype subgroups of Val224Ile polymorphism of GSTM3 gene (p = 0.057 and 0.053, respectively) with the lowest BMD values among heterozygotes and between 224Ile-insAGG haplotype subgroups (p = 0.048 and 0.019, respectively) were found. Significant differences of BMD_fn between the 224Ile-delAGG haplotype subgroups were observed (p = 0.012). Association of 224Val-insAGG with BMD_fn was of borderline significance (p = 0.062). Conclusion: The results of our study demonstrate the genetic association between detoxifying enzyme GSTM3 and BMD variation, suggesting that the Val- 224Ile polymorphism and 224Ile-insAGG haplotype could be used for further evaluation of the impact of GSTs gene polymorphisms on osteoporosis, using larger cohorts in searching for osteoporosis risk markers.

COBISS.SI-ID: 3198833
3.
Specific cognitive abilities are associated with diabetes self-management behaviour among patients with type 2 diabetes.

3. Patients with diabetes differ in compliance to diabetes self-management which influences their long-term health. Psychological factors, namely depression and cognitive abilities, are associated with diabetes self-management behaviour. The aim of the study was to identify independent association of particular cognitive functions with diabetes self-management. In a cross sectional study 98 adults with type 2 diabetes. We found that specific cognitive functions, namely immediate memory, visuospatial/constructional abilities, attention, and specific executive functions (planning and problem solving) were significantly associated with diabetes self-management. Among cognitive factors, planning and problem solving abilities were strongest predictors; furthermore, in a multivariate regression their association their association was independent from depression.

COBISS.SI-ID: 29621721