A missense single nucleotide polymorphism, V114I of the Werner syndrome gene, is associated with risk of osteoporosis and femoral fracture ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2015-01-31

AUTHORS

Heying Zhou, Seijiro Mori, Masashi Tanaka, Motoji Sawabe, Tomio Arai, Masaaki Muramatsu, Makiko Naka Mieno, Shoji Shinkai, Yoshiji Yamada, Motohiko Miyachi, Haruka Murakami, Kiyoshi Sanada, Hideki Ito

ABSTRACT

Werner syndrome is a rare autosomal recessive disorder caused by mutations in the human WRN gene and characterized by the early onset of normal aging symptoms. Given that patients with this disease exhibit osteoporosis, the present study aimed to determine whether the WRN gene contributes to the etiology of osteoporosis. A genetic association study of eight non-synonymous polymorphisms in the WRN gene and the incidence of femoral fracture was undertaken in 1,632 consecutive Japanese autopsies in which 140 patients had experienced the fracture during their lifetime. The results were validated in 251 unrelated postmenopausal Japanese women with osteoporosis and 269 non-institutionalized, community-dwelling Japanese adults. A statistically significant association was observed between rs2230009 (c.340G > A)—which results in a Val to Ile substitution—and fracture risk; the incidence of femoral fracture increased dose-dependently with the number of A alleles (p = 0.0120). Femoral neck bone and whole bone densities were lower among postmenopausal women with osteoporosis and community-dwelling adults, respectively, if they were of the AG instead of the GG genotype. The results suggest that Japanese subjects bearing at least one A allele of rs2230009 of the WRN gene are at a significantly higher risk of femoral fracture, possibly due to decreased bone density. More... »

PAGES

694-700

References to SciGraph publications

Journal

TITLE

Journal of Bone and Mineral Metabolism

ISSUE

6

VOLUME

33

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00774-014-0636-0

DOI

http://dx.doi.org/10.1007/s00774-014-0636-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1020399492

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25637295


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38 schema:description Werner syndrome is a rare autosomal recessive disorder caused by mutations in the human WRN gene and characterized by the early onset of normal aging symptoms. Given that patients with this disease exhibit osteoporosis, the present study aimed to determine whether the WRN gene contributes to the etiology of osteoporosis. A genetic association study of eight non-synonymous polymorphisms in the WRN gene and the incidence of femoral fracture was undertaken in 1,632 consecutive Japanese autopsies in which 140 patients had experienced the fracture during their lifetime. The results were validated in 251 unrelated postmenopausal Japanese women with osteoporosis and 269 non-institutionalized, community-dwelling Japanese adults. A statistically significant association was observed between rs2230009 (c.340G > A)—which results in a Val to Ile substitution—and fracture risk; the incidence of femoral fracture increased dose-dependently with the number of A alleles (p = 0.0120). Femoral neck bone and whole bone densities were lower among postmenopausal women with osteoporosis and community-dwelling adults, respectively, if they were of the AG instead of the GG genotype. The results suggest that Japanese subjects bearing at least one A allele of rs2230009 of the WRN gene are at a significantly higher risk of femoral fracture, possibly due to decreased bone density.
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46 GG genotype
47 Japanese adults
48 Japanese autopsies
49 Japanese population
50 Japanese subjects
51 Japanese women
52 Val
53 WRN gene
54 Werner syndrome
55 Werner syndrome gene
56 adults
57 alleles
58 association
59 association studies
60 autopsies
61 autosomal recessive disorder
62 bone
63 bone density
64 community-dwelling Japanese adults
65 community-dwelling adults
66 density
67 disorders
68 dose
69 early onset
70 etiology
71 etiology of osteoporosis
72 femoral fractures
73 femoral neck bone
74 fracture risk
75 fractures
76 genes
77 genetic association studies
78 genotypes
79 high risk
80 human WRN gene
81 incidence
82 lifetime
83 missense single nucleotide polymorphism
84 mutations
85 neck bone
86 non-synonymous polymorphisms
87 nucleotide polymorphisms
88 number
89 onset
90 osteoporosis
91 patients
92 polymorphism
93 population
94 postmenopausal Japanese women
95 postmenopausal women
96 present study
97 rare autosomal recessive disorder
98 recessive disorder
99 results
100 risk
101 risk of osteoporosis
102 significant association
103 single nucleotide polymorphisms
104 study
105 subjects
106 substitution
107 symptoms
108 syndrome
109 syndrome gene
110 whole bone density
111 women
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