Molecular aspects of osteopathy in type 1 Gaucher disease: correlation between genetics and bone density

Arnheim, Efrat; Chicco, Gaya; Phillips, Mici; Lebel, Ehud; Foldes, A. Joseph; Itzchaki, Menachem; Elstein, Deborah; Zimran, Ari; Altarescu, Gheona

doi:10.1007/s00296-008-0550-7

Cited by 10 publications

(10 citation statements)

References 18 publications

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“…The finding of polymorphisms of genes (CYP1A1, BMP4, and VDR) that have been previously identified as associated with osteoporosis in non-GD populations and which are correlated with low BMD in GD, may implicate a constellation of non-Gaucher specific factors that are as predictive in patients with GD as in other osteoporotic persons [33]. Moreover, one haplotype of IL-1 genes was identified among patients with GD that correlates with osteopathy [33].…”

Section: Clinical and Radiological Aspects Of Bone Manifestationsmentioning

confidence: 93%

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Gaucher Disease and Bone Manifestations

et al. 2014

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Gaucher disease is a relatively rare metabolic disease caused by the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Gaucher disease affects multiple organs, among which is the skeleton. Bone involvement occurs frequently in Gaucher disease, and is one of its most debilitating features, reducing the quality of life of patients. Bone status is an important consideration for treatment to ameliorate symptoms and reduce the risk of irreversible complications. We have conducted a systematic review of all the various aspects of Gaucher disease, focusing on different skeletal manifestations, pathophysiology of bone alterations, clinical symptoms, and current diagnostic and therapeutic approaches.

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Section: Clinical and Radiological Aspects Of Bone Manifestationsmentioning

confidence: 93%

“…Moreover, one haplotype of IL-1 genes was identified among patients with GD that correlates with osteopathy [33].…”

Section: Clinical and Radiological Aspects Of Bone Manifestationsmentioning

confidence: 99%

Gaucher Disease and Bone Manifestations

et al. 2014

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“…The FokI polymorphism of the VDR gene has been associated with BMD in many studies [15]. A similar study looking for genetic modifiers regarding osteoporosis/osteopenia was performed by Arnheim et al [17] in patients with Gaucher Disease. In Gaucher patients FokI polymorphisms were strongly associated with osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

“…The distribution of the Vitamin D receptor Fok I genotypes for PWS patients and controls were: 39 (40.6%) patients were homozygous FF and 28% of controls, 35 (36.5%) patients were heterozygous Ff compared to 58.5% in controls and 22 (22.9%) patients were homozygous for the minor allele ff (13.8% in controls) [17] (Table 5) Age (years) (mean ± SD) 16.6 ± 9.7…”

Section: Discussionmentioning

confidence: 99%

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Bone Mineral Density in Prader Willi Syndrome: A Search for Genetic Markers

Altarescu¹,

Gross-Tsur²,

Hirsch³

et al. 2017

J Osteopor Phys Act

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decreased BMD and bone mineral content (BMC) in PWS. Recently it has been shown that PW Snord 116 knockout mice show reduced bone formation indicating a possible link between the PW critical region and osteoporosis [10]. Since bone density and mineral content are highly variable among PWS individuals, other factors may contribute to the development of osteopenia and/or osteoporosis. Identifying risk factors for developing osteopenia or osteoporosis may allow early intervention prior to severe bone loss. The purpose of our study was to investigate polymorphisms of candidate genes previously shown to correlate with osteoporosis and/or bone disease and determine if similar associations are present in a PWS population. Materials and MethodsDNA samples were collected from 96 of 103 individuals above the age of 3 years with PWS followed at the Israeli national multidisciplinary PWS clinic at Shaare Zedek Medical Center, Jerusalem, Israel. There were Keywords: Prader-Willi syndrome; Osteoporosis; Osteopenia; Genetic markers of osteoporosis; Bone mineral density; DXA IntroductionPrader-Willi syndrome (PWS) is a complex genetic disorder caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. The estimated prevalence is 1/10,000-1/30,000 [1]. Infants with PWS suffer from severe hypotonia, feeding difficulties, and failure to thrive (FTT) followed in later infancy or early childhood by excessive appetite with gradual development of obesity, short stature, hypogonadism, intellectual disabilities and behavioral problems [2].There are three main genetic subtypes in PWS: paternal 15q11-q13 deletion in 65-75%, maternal uniparental disomy (UPD) in 20-30% and imprinting center defect in 1-3% of all cases [3,4]. PWS is the most common syndromic cause of life-threatening obesity and the first recognized disorder related to genomic imprinting. Muscle mass is decreased by 25-37%, which might partly explain the hypotonia [5]. Diabetes and scoliosis are common features of PWS [6]. Hypothalamic dysfunction has been implicated in many manifestations of this syndrome including hyperphagia, high pain threshold, sleepdisordered breathing, and multiple endocrine abnormalities including hypogonadism [7,8]. The etiology of hypogonadism in PWS (primary gonadal or hypothalamic) is heterogeneous [5].Increased fat mass and decreased lean body mass are characteristics of PWS. Several studies have demonstrated that individuals with PWS have lower bone mineral density (BMD) compared to normal controls [9]. Hypotonia, hypogonadism, growth hormone deficiency, and limited mineral and vitamin intake due to diet restrictions may contribute to the Abstract Introduction: Prader-Willi syndrome (PWS (is caused by lack of paternally expressed imprinted genes at chromosome 15q11.2-q13. Diminished (BMD) and osteoporosis are common in PWS. The purpose of this study was to determine whether polymorphisms in genes previously shown to correlate with bone mineral density (BMD), might explain the variable expression of abnormal...

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Effect of vitamin D receptor (VDR) genotypes on the risk for osteoporosis in type 1 Gaucher disease

et al. 2010

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The almost universal finding of osteopenia in Gaucher disease and the unpredictable advent of avascular necrosis and/or pathological fractures are clinically relevant issues that are not necessarily reversed by specific enzyme replacement therapy (ERT). However, genetic/epigenetic factors may explain variance for bone mineral density (BMD) in the normal population. Among the candidate genes, vitamin D receptor (VDR) polymorphisms have been correlated with BMD at the lumbar spine (LS) and femoral neck (FN) and/or fracture risk in various populations. Helsinki Committee approval was received. DNA samples from 15 healthy individuals and 83 non-neuronopathic adult patients with recent BMD data at LS and FN were tested for VDR polymorphisms FokI, ApaI, TaqI, and BsmI. Chi-square, Fisher's exact, analysis of variance (ANOVA), Scheffe post hoc, and non-parametric Kruskal-Wallis ANOVA were applied as appropriate. P values <0.05 was considered statistically significant. There were no significant differences between patients and controls in frequency of any of polymorphic genotypes. The ApaI and BsmI genotypes were correlated with the N370S/N370S Gaucher genotype (p = 0.029, and p = 0.061, respectively). There was a correlation between the BsmI genotype and skeletal involvement (p = 0.018) and a trend to significance with Z scores at LS (p = 0.084). There was a statistically significant correlation between the Taq1 variants and BMD at the FN (p = 0.030) with the TT variant associated with lower BMD. As in other populations, VDR polymorphic genotype may be an independently sorting modifier in the prediction of BMD and bone involvement in Gaucher disease.

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Molecular aspects of osteopathy in type 1 Gaucher disease: correlation between genetics and bone density

Cited by 10 publications

References 18 publications

Gaucher Disease and Bone Manifestations

Gaucher Disease and Bone Manifestations

Bone Mineral Density in Prader Willi Syndrome: A Search for Genetic Markers

Effect of vitamin D receptor (VDR) genotypes on the risk for osteoporosis in type 1 Gaucher disease

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