Association of a Single Nucleotide Polymorphism in the Insulin-Like Growth Factor-1 Receptor Gene With Spinal Disc Degeneration in Postmenopausal Japanese Women

Urano, Tomohiko; Narusawa, Kenichiro; Shiraki, Masataka; Usui, Takahiko; Sasaki, Noriko; Hosoi, Takayuki; Ouchi, Yasuyoshi; Nakamura, Toshio; Inoue, Satoshi

doi:10.1097/brs.0b013e3181715304

Cited by 30 publications

(29 citation statements)

References 45 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Attempting to elucidate the pathogenesis of lower back pain, we previously investigated the association of various genetic factors with spinal degeneration [23][24][25][26]. In our previous studies on the common genetic variants associated with spinal degeneration, we found that polymorphism of the LRP5 gene correlated with osteophyte formation [26], while that of the IGF1R correlated with disc space narrowing [25]. Here, we demonstrated that Japanese postmenopausal women with two T alleles at intron 2 of the HAPLN1 gene had significantly higher scores for both osteophyte formation and disc space narrowing.…”

Section: Discussionmentioning

confidence: 99%

“…Both lateral projections in the lateral decubitus position and A-P projections in the supine position were obtained at a constant focus-film distance of 1.5 m. The severity of spinal degeneration, including osteophyte formation, endplate sclerosis, and disc space narrowing, was semiquantitatively assessed from the T4/5 to L4/5 disc level or from the T4 to L4 level using the grading scale described by Genant [31]. Next, we radiographically assessed spinal disc degeneration by using a previously reported scoring system [23][24][25][26]. In brief, osteophyte formation at a particular disc level was graded 0-3 degrees; endplate sclerosis, 0-2 degrees; disc space narrowing, 0-1 degree.…”

Section: Radiographic Grading Of Spinal Disc Degenerationmentioning

confidence: 99%

“…We identified these four SNPs in the HAPLN1 gene by using the TaqMan (Applied Biosystems) polymerase chain reaction (PCR) method [23][24][25][26]. To identify an SNP in HAPLN1, we used Assays-on-Demand SNP genotyping products, which include sequence-specific forward and reverse primers and two TaqMan MGB probes for detecting alleles.…”

Section: Radiographic Grading Of Spinal Disc Degenerationmentioning

confidence: 99%

See 2 more Smart Citations

Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women

Urano

Narusawa

Shiraki³

et al. 2010

Eur Spine J

Self Cite

View full text Add to dashboard Cite

Spinal osteoarthritis including disc degeneration is a very common condition in the axial skeletons of aged people. Recently, spinal osteoarthritis has been shown to be influenced by specific genetic risk factors. Vertebral osteophytes, endplate sclerosis, and intervertebral disc narrowing are recognized as radiographic features of spinal disc degeneration. HAPLN1 is a key component of the cartilage extracellular matrix; thus, variations in this gene may affect the pathogenesis of cartilage-related diseases such as spinal degeneration. Here, we examine the association between an HAPLN1 gene polymorphism and the radiographic features of spinal degeneration. We evaluated the degree of endplate sclerosis, osteophyte formation, and disc space narrowing in 622 Japanese postmenopausal women. Four SNPs in the HAPLN1 gene-in the 5 0 flanking region, intron 1, intron 2, and intron 4-were analyzed using the TaqMan polymerase chain reaction method. We found that compared to subjects with the CC or CT genotype, those with the TT genotype for an SNP at intron 2 (rs179851) were significantly overrepresented among the subjects with higher scores for osteophyte formation (P = 0.0001; odds ratio 2.12; 95% confidence interval 1.45-3.11, as determined by logistic regression analysis) and disc space narrowing (P = 0.0057; odds ratio 1.83; 95% confidence interval 1.19-2.83). Consistent with the involvement of the HAPLN1 gene in cartilage metabolism, a variation in a specific HAPLN1 gene locus may be associated with spinal degeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Radiographic Grading Of Spinal Disc Degenerationmentioning

confidence: 99%

Section: Radiographic Grading Of Spinal Disc Degenerationmentioning

confidence: 99%

See 1 more Smart Citation

Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women

Urano

Narusawa

Shiraki³

et al. 2010

Eur Spine J

Self Cite

View full text Add to dashboard Cite

show abstract

“…The association between the A1330V polymorphism of the LRP5 gene and BMD has been studied in several groups [18][19][20][21]. In these studies, BMD was measured at the lumbar spine, the femoral neck, and the trochanter, however, the total body BMD was not measured.…”

Section: Acknowledgmentsmentioning

confidence: 99%

“…We determined the A1330V (c.3989C>T) polymorphism of the LRP5 gene using the TaqMan (Applied Biosystems) polymerase chain reaction (PCR) method [20]. To determine the LRP5 SnP, we used an Assayson-Demand SnP Genotyping kit C__25752205_10 in embryonic development and oncogenesis [10,11].…”

Section: Determination Of a Snp In The Lrp5 Genementioning

confidence: 99%

A1330V Variant of the Low-density Lipoprotein Receptorrelated Protein 5 (LRP5) Gene Decreases Wnt Signaling and Affects the Total Body Bone Mineral Density in Japanese Women

Urano

Shiraki²,

Usui

et al. 2009

Endocr J

Self Cite

View full text Add to dashboard Cite

gate phenotype used in the research for osteoporosis. BMD is a complex trait that is influenced by both genetic and environmental factors. Heritability studies in families and studies of twins have shown that genetic factors account for 50%-90% of the variance in BMD [2][3][4][5][6]. So far, several genes for osteoporosis have been established. These genes include the vitamin D receptor (VDR) gene [7], estrogen receptor α (ERα) gene [8], and collagen type Iα1 (COLIA1) gene [9]. We need to clarify more genetic factors of BMD, considering the polygenetic nature of BMD distribution and the multiplicity of endocrine factors known to regulate bone mass and bone turnover.The Wnt signaling pathway plays a important role , and is associated with lumbar spine, femoral neck, and radial bone mineral density (BMD), and incidence of fracture. These data suggest that the A1330V variation in the LRP5 gene may affect the pathogenesis of osteoporosis. However, the functional basis of the A1330V variation remains unclear. In the present study, we analyzed the effect of the A1330V variation on Wnt activity. We also investigated the association between this LRP5 SnP and total body BMD using 739 postmenopausal women. LRP5 with the A1330V SnP were transiently coexpressed with Wnt3a in 293T cells and their activity was evaluated by the TCF-Lef reporter assay. In vitro, the TCF-Lef activity in presence of Wnt3a in cells expressing LRP5 and carrying the T allele (Valine at 1330 (V1330)) of exon 18 was significantly reduced as compared to the wild-type allele. The association between the A1330V SnP and total body BMD were replicated in 739 postmenopausal Japanese women (AA vs. VV; P = 0.0026). These data suggest that the V1330 variant in the LRP5 gene decreases Wnt activity, which in turn decreases the BMD.

show abstract

Pathomechanism of intervertebral disc degeneration

et al. 2020

View full text Add to dashboard Cite

Intervertebral disc degeneration (IDD) is the main contributor to low back pain, which is a leading cause of disability worldwide. Although substantial progress has been made in elucidating the molecular mechanisms of IDD, fundamental and long‐lasting treatments for IDD are still lacking. With increased understanding of the complex pathomechanism of IDD, alternative strategies for treating IDD can be discovered. A brief overview of the prevalence and epidemiologic risk factors of IDD is provided in this review, followed by the descriptions of anatomic, cellular, and molecular structure of the intervertebral disc as well as the molecular pathophysiology of IDD. Finally, the recent findings of intervertebral disc progenitors are reviewed and the future perspectives are discussed.

show abstract

Association of a Single Nucleotide Polymorphism in the Insulin-Like Growth Factor-1 Receptor Gene With Spinal Disc Degeneration in Postmenopausal Japanese Women

Abstract: We suggest that a genetic variation at the IGF1R gene locus is associated with spinal disc degeneration, in line with the involvement of the IGF1R gene in the cartilage metabolism.

Cited by 30 publications

References 45 publications

Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women

Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women

A1330V Variant of the Low-density Lipoprotein Receptorrelated Protein 5 (LRP5) Gene Decreases Wnt Signaling and Affects the Total Body Bone Mineral Density in Japanese Women

Pathomechanism of intervertebral disc degeneration

Contact Info

Product

Resources

About