Journal of Pathology and Translational Medicine

Original Articles

TNF-α and TNF-β Polymorphisms are Associated with Susceptibility to Osteoarthritis in a Korean Population: Lin Han, Joo Hyoun Song, Jung Hwan Yoon, Yong Gyu Park, Suk Woo Lee, Yoo Jin Choi, Suk Woo Nam, Jung Young Lee, Won Sang Park; Korean J Pathol. 2012;46(1):30-37. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.30

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Background

The tumor necrosis factor (TNF) is believed to play an important role in the pathophysiology of osteoarthritis (OA). Evidence shows that genetic polymorphisms make substantial contributions to the etiology of OA.

Methods

We investigated the genotypes TNF-α and TNF-β in 301 OA patients and 291 healthy subjects as controls. We employed a polymerase chain reaction-restriction fragment length polymorphism and a polymerase chain reaction-single strand conformation polymorphism assay to identify the genotypes TNFA -G308A and TNFB +G252A, respectively.

Results

For TNFA -G308A, the percentages of genotypes GG, AG, and AA were 26.3% (79/301), 62.5% (188/301), and 11.3% (34/301) in OA patients and 88.7% (258/291), 11.3% (33/291), and 0% (0/291) in controls. For TNFB +G252A, the percentages of genotypes GG, AG, and AA were 15.3% (46/301), 41.9% (126/301), and 42.9% (129/301) in OA patients and 12% (35/291), 52.6% (153/291), and 35.4% (103/291) in controls. There were significant differences in genotypes and alleles of TNFA -308 between OA patients and controls (p<0.0001) and in alleles of TNFB +252 (p=0.0325). The risk of OA was significantly higher for carriers of the TNFA -308A allele and the TNFB +252 AA homozygote (p=0.0224).

Conclusions

The results suggest close relationships between TNFA -G308A and TNFB +G252A polymorphisms and individual susceptibility to OA in the Korean population.

Citations

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Growth Differentiation Factor 5 (GDF5) Core Promoter Polymorphism Is Not Associated with Susceptibility to Osteoarthritis of the Knee in the Korean Population.: Zhang Cao, Hwa Sung Lee, Jae Hwi Song, Jeong Whan Yoon, Yong Kyu Park, Suk Woo Nam, Jung Young Lee, Won Sang Park; Korean J Pathol. 2010;44(4):404-409.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.404

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Abstract PDF

BACKGROUND
Osteoarthritis (OA) is a common disease characterized by degenerating joint cartilage in the knee, hip, and hand. A functional single nucleotide polymorphism (SNP) +104T/C; rs143383 in the 5' untranslated region of the growth differentiation factor 5 (GDF5) gene was recently associated with susceptibility to OA in the Japanese and Chinese populations.
METHODS
To investigate whether this association is present in the Korean population, the frequency of the polymorphism was investigated in 276 patients with knee OA and 298 healthy subjects as controls. Polymorphism analysis was performed by amplifying the core promoter region of the GDF5 gene and digesting it with the BsiEI restriction enzyme.
RESULTS
The frequency of the TT, CT, and CC genotypes was 54.3% (150/276), 41.7% (115/276), and 4.0% (11/276), respectively, in patients with OA, and 53.4% (159/298), 37.9% (113/298), and 8.7% (26/298), respectively, in healthy controls. No significant differences in genotypic or allelic frequencies of the +104T/C SNP of the GDF5 gene were observed between patients with OA and controls. Also, no significant differences in allelic and genotypic frequencies were found when the individuals were stratified by age and gender.
CONCLUSIONS
The results suggest that the +104T/C; rs143383 GDF5 core promoter polymorphism is not a risk factor for OA in the Korean population.

Citations

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Correlation of growth differentiation factor-5 + 104T>C polymorphism with the risk of knee, hand, and hip osteoarthritis: a case-control study and meta-analysis based on 47 case-control studies
Kamran Alijanpour, Seyed Alireza Dastgheib, Leila Azizi, Amirmasoud Shiri, Mohammad Bahrami, Maryam Aghasipour, Somaye Miri, Kazem Aghili, Zinatalsadat Dehghani-Manshadi, Hossein Neamatzadeh, Sahel Khajehnoori
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Association between the +104T/C polymorphism in the 5′UTR of GDF5 and susceptibility to knee osteoarthritis: A meta-analysis
SHAO-WEN HAO, QUN-HUA JIN
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A genetic association study between growth differentiation factor 5 (GDF 5) polymorphism and knee osteoarthritis in Thai population
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Expression of Matrix Metalloproteinase (MMP)-1, MMP-3 Nitrotyrosine and Apoptosis in Articular Cartilage of Human Osteoarthritis.: So Young Jin, Seong Su Kang, Dong Wha Lee, Soo Jae Yim, Yeo Hon Yun, Byung Ill Lee; Korean J Pathol. 2001;35(4):319-329.

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Abstract PDF: BACKGROUND
Matrix metalloproteinase (MMP)-1 and 3 are the most important degradating enzymes of the chondroid matrix. Chondrocytes may undergo apoptosis under various stimuli including nitric oxide (NO). We studied the expression rate and zone of MMP-1, MMP-3, nitrotyrosine, a marker of NO release, and apoptosis in the articular cartilage of human osteoarthritis.
METHODS
To investigate the role of nitrotyrosine and apoptosis in the degradation of the chondroid matrix in human osteoarthritis, immunohistochemistry was done for MMP-1, MMP-3, and nitrotyrosine; and the terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) method was performed for apoptosis using a total of 93 articular cartilages from 12 femoral heads and 17 knees obtained from total joint arthroplasty and 7 normal articular cartilages. RESULTS: In the normal control group, the expression rates for MMP-1, MMP-3, nitrotyrosine, and apoptosis were very low; and their expression zones were confined to the superficial layer of the articular cartilage. Their expression rates were low in the early stage of osteoarthritis and were moderate to high in the late stage (P<0.05). Their expression zones were confined to the superficial layer of the articular cartilage in the early stage of osteoarthritis and were expressed throughout the whole layer in the late stage and those of MMP-3 and nitrotyrosine were statistically significant (P<0.05). Their expression rates and zones were significantly correlated with the grade of osteoarthritis (P<0.05). Conclusion : The expression rate and zone of apoptosis and nitrotyrosine correlated well with those of MMP-1 and MMP-3. Therefore, NO and apoptosis may be related to the progression of human osteoarthritis.

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