Редактирование: DKK2

Dickkopf-related protein 2 precursor (Dickkopf-2) (Dkk-2) (hDkk-2) [UNQ682/PRO1316]

==Publications==

{{medline-entry
|title=Low Serum Levels of [[DKK2]] Predict Incident Low-Impact Fracture in Older Women.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31372588
|abstract=There are currently no robust noninvasive markers of fragility fractures. Secreted frizzled related protein-1 (sFRP-1), dickkopf-related protein 1 ([[DKK1]]) and [[DKK2]], and sclerostin ([[SOST]]) inhibit Wnt signaling and interfere with osteoblast-mediated bone formation. We evaluated associations of serum levels of sFRP-1, [[DKK1]], [[DKK2]], and [[SOST]] with incident low-impact fracture and BMD in 828 women aged ≥65 years from EpiDoC, a longitudinal population-based cohort. A structured questionnaire during a baseline clinical appointment assessed prevalent fragility fractures and clinical risk factors (CRFs) for fracture. Blood was collected to measure serum levels of bone turnover markers and Wnt regulators. Lumbar spine and hip BMD were determined by DXA scanning. Follow-up assessment was performed through a phone interview; incident fragility fracture was defined by any new self-reported low-impact fracture. Multivariate Cox proportional hazard models were used to analyze fracture risk adjusted for CRFs and BMD. During a mean follow-up of 2.3 ± 1.0 years, 62 low-impact fractures were sustained in 58 women. A low serum [[DKK2]] level (per 1 SD decrease) was associated with a 1.5-fold increase in fracture risk independently of BMD and CRFs. Women in the two lowest [[DKK2]] quartiles had a fracture incidence rate of 32 per 1000 person-years, whereas women in the two highest quartiles had 14 fragility fractures per 1000 person-years. A high serum sFRP1 level was associated with a 1.6-fold increase in fracture risk adjusted for CRFs, but not independently of BMD. Serum levels of [[SOST]] ([i]r[/i] = 0.191; [i]p[/i] = 0.0025) and [[DKK1]]([i]r[/i] = -0.1725; [i]p[/i] = 0.011) were correlated with hip BMD, but not with incident fragility fracture. These results indicate that serum [[DKK2]] and sFRP1 may predict low-impact fracture. The low number of incident fractures recorded is a limitation and serum levels of Wnt regulators should be further studied in other populations as potential noninvasive markers of fragility fractures. © 2019 The Authors. [i]JBMR Plus[/i] published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

|keywords=* AGING
* FRACTURE RISK ASSESSMENT
* MOLECULAR PATHWAYS–REMODELING
* SCREENING
* Wnt/β‐CATENIN/LRPs
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659448
}}
{{medline-entry
|title=Genome wide association and linkage analyses identified three loci-4q25, 17q23.2, and 10q11.21-associated with variation in leukocyte telomere length: the Long Life Family Study.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24478790
|abstract=Leukocyte telomere length is believed to measure cellular aging in humans, and short leukocyte telomere length is associated with increased risks of late onset diseases, including cardiovascular disease, dementia, etc. Many studies have shown that leukocyte telomere length is a heritable trait, and several candidate genes have been identified, including [[TERT]], TERC, OBFC1, and [[CTC1]]. Unlike most studies that have focused on genetic causes of chronic diseases such as heart disease and diabetes in relation to leukocyte telomere length, the present study examined the genome to identify variants that may contribute to variation in leukocyte telomere length among families with exceptional longevity. From the genome wide association analysis in 4,289 LLFS participants, we identified a novel intergenic SNP rs7680468 located near [[PAPSS1]] and [[DKK2]] on 4q25 (p = 4.7E-8). From our linkage analysis, we identified two additional novel loci with HLOD scores exceeding three, including 4.77 for 17q23.2, and 4.36 for 10q11.21. These two loci harbor a number of novel candidate genes with SNPs, and our gene-wise association analysis identified multiple genes, including [[DCAF7]], [[POLG2]], [[CEP95]], and [[SMURF2]] at 17q23.2; and [[RASGEF1A]], [[HNRNPF]], ANF487, [[CSTF2T]], and [[PRKG1]] at 10q11.21. Among these genes, multiple SNPs were associated with leukocyte telomere length, but the strongest association was observed with one contiguous haplotype in [[CEP95]] and [[SMURF2]]. We also show that three previously reported genes-TERC, [[MYNN]], and OBFC1-were significantly associated with leukocyte telomere length at p empirical < 0.05. 

|keywords=* aging
* familial longevity
* family-based study
* genome wide association and linkage
* novel genes
* telomere length
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894567
}}