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The A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene (LRP5) associates with low peak bone mass in young healthy men.

https://arctichealth.org/en/permalink/ahliterature165637
Source
Bone. 2007 Apr;40(4):1006-12
Publication Type
Article
Date
Apr-2007
Author
Anne Saarinen
Ville-Valtteri Välimäki
Matti J Välimäki
Eliisa Löyttyniemi
Kirsi Auro
Piia Uusen
Mairi Kuris
Anna-Elina Lehesjoki
Outi Mäkitie
Author Affiliation
Folkhälsan Institute of Genetics and Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
Source
Bone. 2007 Apr;40(4):1006-12
Date
Apr-2007
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Alleles
Bone Density - genetics
Calcifediol - blood
Finland
Fractures, Bone - etiology - genetics
Gene Frequency
Humans
LDL-Receptor Related Proteins - genetics
Low Density Lipoprotein Receptor-Related Protein-5
Male
Military Personnel
Osteoporosis - etiology - genetics
Parathyroid Hormone - blood
Polymorphism, Single Nucleotide
Risk factors
Abstract
Polymorphisms in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) contribute to variation in bone mass in the general population. Whether this is due to influence on bone mass acquisition or on bone loss thereafter has not been established.
We studied the association of LRP5 polymorphisms with peak bone mass in young men. The study included 235 Finnish men, aged 18.3 to 20.6 years. Lifestyle factors and fracture history were recorded. Bone mineral content (BMC), density (BMD) and scan area were measured for the lumbar spine and proximal femur by dual energy X-ray absorptiometry (DXA). Blood and urine were collected for determination of bone turnover markers, serum 25-OHD and PTH. Genomic DNA was extracted from peripheral blood for genetic analysis of LRP5. Ten single nucleotide polymorphisms in LRP5 were analyzed and correlated with bone parameters.
Only the A1330V polymorphism of LRP5 significantly associated with bone parameters. In comparison with subjects with the AlaAla genotype (n=215), those with AlaVal genotype (n=20) had lower femoral neck BMC (P=0.029) and BMD (P=0.012), trochanter BMC (P=0.0067) and BMD (P=0.015), and total hip BMC (P=0.0044) and BMD (P=0.0089). Fracture history was similar for the genotypes.
The polymorphic valine variant at position 1330 of LRP5 was significantly associated with reduced BMC and BMD values in healthy young Finnish men. The results provide evidence for the crucial role of LRP5 in peak bone mass acquisition.
PubMed ID
17223614 View in PubMed
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Body composition and bone mineral density in children with premature adrenarche and the association of LRP5 gene polymorphisms with bone mineral density.

https://arctichealth.org/en/permalink/ahliterature148293
Source
J Clin Endocrinol Metab. 2009 Nov;94(11):4144-51
Publication Type
Article
Date
Nov-2009
Author
Pauliina Utriainen
Jarmo Jääskeläinen
Anne Saarinen
Esko Vanninen
Outi Mäkitie
Raimo Voutilainen
Author Affiliation
Departments of Pediatrics, University of Kuopio and Kuopio University Hospital, FI-70211 Kuopio, Finland. pauliina.utriainen@uku.fi
Source
J Clin Endocrinol Metab. 2009 Nov;94(11):4144-51
Date
Nov-2009
Language
English
Publication Type
Article
Keywords
Adrenarche - genetics
Body Composition
Bone Density - genetics
Child
Cross-Sectional Studies
Female
Femur Neck - anatomy & histology
Finland
Humans
LDL-Receptor Related Proteins - genetics
Low Density Lipoprotein Receptor-Related Protein-5
Male
Pituitary Gland - growth & development
Polymorphism, Genetic
Reference Values
Spine - anatomy & histology
Abstract
Precocious increase in adrenal androgen production is the hallmark of premature adrenarche (PA). Adrenal androgens have anabolic properties.
The objective of the study was to test whether body composition and bone mineral density (BMD) are altered in PA and study whether genetic variation in low-density lipoprotein receptor-related protein 5 (LRP5) affects BMD in PA.
This was a cross-sectional study.
The study was conducted at a university hospital.
The study included 126 prepubertal children (64 with PA, 10 boys; 62 non-PA controls, 10 boys). Femoral neck and lumbar spine areal and calculated volumetric BMD (dual energy X-ray absorptiometry), body composition (bioimpedance), serum 25-hydroxyvitamin D, and markers of bone turnover and calcium homeostasis were compared between the PA and control groups. Single-nucleotide polymorphisms of LRP5 were determined and associated with BMD.
Children with PA had higher femoral neck and lumbar spine BMD(areal) than the controls (Z-score 0.56 vs. -0.09, P
PubMed ID
19789208 View in PubMed
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Cerebroretinal microangiopathy with calcifications and cysts: characterization of the skeletal phenotype.

https://arctichealth.org/en/permalink/ahliterature134950
Source
Am J Med Genet A. 2011 Jun;155A(6):1322-8
Publication Type
Article
Date
Jun-2011
Author
Sanna Toiviainen-Salo
Tarja Linnankivi
Anne Saarinen
Mervi K Mäyränpää
Riitta Karikoski
Outi Mäkitie
Author Affiliation
Helsinki Medical Imaging Center, Helsinki University Hospital, Finland. sanna.toiviainen-salo@fimnet.fi
Source
Am J Med Genet A. 2011 Jun;155A(6):1322-8
Date
Jun-2011
Language
English
Publication Type
Article
Keywords
Bone Density
Bone Diseases, Metabolic - physiopathology
Bone and Bones - radiography
Calcinosis - pathology
Central Nervous System Cysts - pathology
DNA Mutational Analysis
Finland
Growth Disorders - physiopathology
Humans
LDL-Receptor Related Proteins - genetics
Leukoencephalopathies - pathology
Low Density Lipoprotein Receptor-Related Protein-5
Mutation - genetics
Phenotype
Retinal Vessels - abnormalities
Syndrome
Abstract
Cerebral cysts and calcifications with leukoencephalopathy and retinal vascular abnormalities are diagnostic hallmarks of cerebroretinal microangiopathy with calcifications and cysts (CRMCC). Previous studies have suggested that skeletal involvement is also common, but its characteristics remain unknown. This study aimed to assess the skeletal phenotype in CRMCC. All Finnish patients with features consistent with CRMCC and for whom radiographs were available were included. Clinical information pertinent to the skeletal phenotype was collected from hospital records, and all plain radiographs were reviewed for skeletal features. Bone mineral density (BMD) was measured by DXA. In one patient, bone biopsies were obtained for bone histology and histomorphometric analyses. The LRP5 gene was analyzed for mutations by direct sequencing. Our results show that the skeletal phenotype in CRMCC includes (1) compromised longitudinal growth pre- and postnatally, (2) generalized osteopenia or early onset low turnover osteoporosis with fragility fractures, and (3) metaphyseal abnormalities that may lead to limb deformities such as short femoral neck or genua valga. DXA measurements in three patients showed low BMD, and bone biopsies in the fourth patient with pathological fractures and impaired fracture healing showed low-turnover osteoporosis, with reduced osteoclast and osteoblast activity. Direct sequencing of all LRP5 coding exons and exon-intron boundaries in six patients with CRMCC revealed no putative mutations. We conclude that the CRMCC-associated bone disease is characterized by low BMD and pathological fractures with delayed healing, metaphyseal changes, and short stature pre- and postnatally. LRP5 is not a disease-causing gene in CRMCC.
PubMed ID
21523908 View in PubMed
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LRP5 in premature adrenarche and in metabolic characteristics of prepubertal children.

https://arctichealth.org/en/permalink/ahliterature155539
Source
Clin Endocrinol (Oxf). 2009 May;70(5):725-31
Publication Type
Article
Date
May-2009
Author
Saila Lappalainen
Anne Saarinen
Pauliina Utriainen
Raimo Voutilainen
Jarmo Jääskeläinen
Outi Mäkitie
Author Affiliation
Department of Paediatrics, Kuopio University and University Hospital, Kuopio, Finland. saila.lappalainen@uku.fi
Source
Clin Endocrinol (Oxf). 2009 May;70(5):725-31
Date
May-2009
Language
English
Publication Type
Article
Keywords
Adrenarche - genetics - metabolism
Alleles
Case-Control Studies
Child
Cross-Sectional Studies
Female
Finland
Gene Frequency
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
LDL-Receptor Related Proteins - genetics
Lipids - blood
Low Density Lipoprotein Receptor-Related Protein-5
Male
Metabolic Syndrome X - etiology - genetics - metabolism
Phenotype
Polymorphism, Single Nucleotide
Signal Transduction
Wnt Proteins - metabolism
Abstract
Premature adrenarche (PA) is associated with unfavourable metabolic characteristics. We hypothesized that genetic variation in low density lipoprotein (LDL) receptor-related protein 5 (LRP5), which is involved in Wnt signalling in the adrenal cortex and in cholesterol metabolism, plays a role in the pathogenesis of PA.
We performed a cross-sectional association study in 73 Finnish children with PA and 97 age- and gender-matched healthy controls.
LRP5 genotypes were determined by direct sequencing. Single-marker associations with clinical-metabolic characteristics, including adrenocortical function, glucose tolerance and lipid profile, were examined with age and gender as covariates.
Nineteen single nucleotide polymorphisms (SNPs) in LRP5 were found in the 170 children. No significant differences in the genotype distributions were observed between the PA and control groups. SNPs A1330V and N740N were associated with higher serum dehydroepiandrosterone sulphate (DHEAS) levels in the control subjects (A/A vs. A/a; mean 0.8 vs. 1.4 micromol/l, P = 0.01). They were also associated with higher plasma levels of total (4.2 vs. 4.7 mmol/l, P = 0.02) and LDL cholesterol (2.4 vs. 2.9 mmol/l, P = 0.02) in the control group, as was SNP V1119V (P = 0.04 and P = 0.03, respectively). SNPs F549F and V1119V were associated with higher systolic blood pressure (P = 0.04 and P = 0.02, respectively). There were no differences in the parameters of glucose metabolism between the genotype groups.
Genetic variation in LRP5 did not predispose to PA but was associated with metabolic characteristics, especially lipid profile, in healthy prepubertal children.
PubMed ID
18721193 View in PubMed
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