An intron polymorphism of the fibronectin gene is associated with end-stage knee osteoarthritis in a Han Chinese population: Two independent case - Control studies

Hsin Yi Yang, Sui Lung Su, Yi Jen Peng, Chih Chien Wang, Herng Sheng Lee, Donald M. Salter, Chian Her Lee

Research output: Contribution to journalArticle

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Abstract

Background: Knee osteoarthritis (OA) is a complex disease involving both biomechanical and metabolic factors that alter the tissue homeostasis of articular cartilage and subchondral bone. The catabolic activities of extracellular matrix degradation products, especially fibronectin (FN), have been implicated in mediating cartilage degradation. Chondrocytes express several members of the integrin family which can serve as receptors for FN including integrins 5β1, vβ3, and vβ5. The purpose of this study was to determine whether polymorphisms in the FN (FN-1) and integrin genes are markers of susceptibility to, or severity of, knee OA in a Han Chinese population. Methods. Two independent case-control studies were conducted on 928 patients with knee OA and 693 healthy controls. Ten single nucleotide polymorphisms (SNPs) of FN-1 and the integrin V gene (ITGAV) were detected using the ABI 7500 real-time PCR system. Results: The AT heterozygote in FN-1 (rs940739A/T) was found to be significantly associated with knee OA (adjusted OR = 1.44; 95% CI = 1.16-1.80) in both stages of the study. FN-1 rs6725958C/A and ITGAV rs10174098A/G SNPs were only associated with knee OA when both study groups were combined. Stratifying the participants by Kellgren-Lawrence (KL) score identified significant differences in the FN-1 rs6725958C/A and rs940739 A/T genotypes between patients with grade 4 OA and controls. Haplotype analyses revealed that TGA and TAA were associated with a higher risk of OA, and that TAG conferred a lower risk of knee OA in the combined population. Conclusions: Our study suggests that the FN-1 rs940739A/T polymorphism may be an important risk factor of genetic susceptibility to knee OA in the Han Chinese population.

Original languageEnglish
Article number173
JournalBMC Musculoskeletal Disorders
Volume15
Issue number1
DOIs
Publication statusPublished - May 23 2014

Fingerprint

Knee Osteoarthritis
Fibronectins
Introns
Case-Control Studies
Integrins
Population
Genes
Osteoarthritis
Single Nucleotide Polymorphism
Fibronectin Receptors
Computer Systems
Articular Cartilage
Thromboplastin
Genetic Predisposition to Disease
Heterozygote
Chondrocytes
Haplotypes
Cartilage
Extracellular Matrix
Real-Time Polymerase Chain Reaction

Keywords

  • Fibronectin gene
  • Integrin V gene
  • Knee osteoarthritis
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Rheumatology
  • Medicine(all)

Cite this

An intron polymorphism of the fibronectin gene is associated with end-stage knee osteoarthritis in a Han Chinese population : Two independent case - Control studies. / Yang, Hsin Yi; Su, Sui Lung; Peng, Yi Jen; Wang, Chih Chien; Lee, Herng Sheng; Salter, Donald M.; Lee, Chian Her.

In: BMC Musculoskeletal Disorders, Vol. 15, No. 1, 173, 23.05.2014.

Research output: Contribution to journalArticle

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abstract = "Background: Knee osteoarthritis (OA) is a complex disease involving both biomechanical and metabolic factors that alter the tissue homeostasis of articular cartilage and subchondral bone. The catabolic activities of extracellular matrix degradation products, especially fibronectin (FN), have been implicated in mediating cartilage degradation. Chondrocytes express several members of the integrin family which can serve as receptors for FN including integrins 5β1, vβ3, and vβ5. The purpose of this study was to determine whether polymorphisms in the FN (FN-1) and integrin genes are markers of susceptibility to, or severity of, knee OA in a Han Chinese population. Methods. Two independent case-control studies were conducted on 928 patients with knee OA and 693 healthy controls. Ten single nucleotide polymorphisms (SNPs) of FN-1 and the integrin V gene (ITGAV) were detected using the ABI 7500 real-time PCR system. Results: The AT heterozygote in FN-1 (rs940739A/T) was found to be significantly associated with knee OA (adjusted OR = 1.44; 95{\%} CI = 1.16-1.80) in both stages of the study. FN-1 rs6725958C/A and ITGAV rs10174098A/G SNPs were only associated with knee OA when both study groups were combined. Stratifying the participants by Kellgren-Lawrence (KL) score identified significant differences in the FN-1 rs6725958C/A and rs940739 A/T genotypes between patients with grade 4 OA and controls. Haplotype analyses revealed that TGA and TAA were associated with a higher risk of OA, and that TAG conferred a lower risk of knee OA in the combined population. Conclusions: Our study suggests that the FN-1 rs940739A/T polymorphism may be an important risk factor of genetic susceptibility to knee OA in the Han Chinese population.",
keywords = "Fibronectin gene, Integrin V gene, Knee osteoarthritis, Single nucleotide polymorphism",
author = "Yang, {Hsin Yi} and Su, {Sui Lung} and Peng, {Yi Jen} and Wang, {Chih Chien} and Lee, {Herng Sheng} and Salter, {Donald M.} and Lee, {Chian Her}",
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T1 - An intron polymorphism of the fibronectin gene is associated with end-stage knee osteoarthritis in a Han Chinese population

T2 - Two independent case - Control studies

AU - Yang, Hsin Yi

AU - Su, Sui Lung

AU - Peng, Yi Jen

AU - Wang, Chih Chien

AU - Lee, Herng Sheng

AU - Salter, Donald M.

AU - Lee, Chian Her

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N2 - Background: Knee osteoarthritis (OA) is a complex disease involving both biomechanical and metabolic factors that alter the tissue homeostasis of articular cartilage and subchondral bone. The catabolic activities of extracellular matrix degradation products, especially fibronectin (FN), have been implicated in mediating cartilage degradation. Chondrocytes express several members of the integrin family which can serve as receptors for FN including integrins 5β1, vβ3, and vβ5. The purpose of this study was to determine whether polymorphisms in the FN (FN-1) and integrin genes are markers of susceptibility to, or severity of, knee OA in a Han Chinese population. Methods. Two independent case-control studies were conducted on 928 patients with knee OA and 693 healthy controls. Ten single nucleotide polymorphisms (SNPs) of FN-1 and the integrin V gene (ITGAV) were detected using the ABI 7500 real-time PCR system. Results: The AT heterozygote in FN-1 (rs940739A/T) was found to be significantly associated with knee OA (adjusted OR = 1.44; 95% CI = 1.16-1.80) in both stages of the study. FN-1 rs6725958C/A and ITGAV rs10174098A/G SNPs were only associated with knee OA when both study groups were combined. Stratifying the participants by Kellgren-Lawrence (KL) score identified significant differences in the FN-1 rs6725958C/A and rs940739 A/T genotypes between patients with grade 4 OA and controls. Haplotype analyses revealed that TGA and TAA were associated with a higher risk of OA, and that TAG conferred a lower risk of knee OA in the combined population. Conclusions: Our study suggests that the FN-1 rs940739A/T polymorphism may be an important risk factor of genetic susceptibility to knee OA in the Han Chinese population.

AB - Background: Knee osteoarthritis (OA) is a complex disease involving both biomechanical and metabolic factors that alter the tissue homeostasis of articular cartilage and subchondral bone. The catabolic activities of extracellular matrix degradation products, especially fibronectin (FN), have been implicated in mediating cartilage degradation. Chondrocytes express several members of the integrin family which can serve as receptors for FN including integrins 5β1, vβ3, and vβ5. The purpose of this study was to determine whether polymorphisms in the FN (FN-1) and integrin genes are markers of susceptibility to, or severity of, knee OA in a Han Chinese population. Methods. Two independent case-control studies were conducted on 928 patients with knee OA and 693 healthy controls. Ten single nucleotide polymorphisms (SNPs) of FN-1 and the integrin V gene (ITGAV) were detected using the ABI 7500 real-time PCR system. Results: The AT heterozygote in FN-1 (rs940739A/T) was found to be significantly associated with knee OA (adjusted OR = 1.44; 95% CI = 1.16-1.80) in both stages of the study. FN-1 rs6725958C/A and ITGAV rs10174098A/G SNPs were only associated with knee OA when both study groups were combined. Stratifying the participants by Kellgren-Lawrence (KL) score identified significant differences in the FN-1 rs6725958C/A and rs940739 A/T genotypes between patients with grade 4 OA and controls. Haplotype analyses revealed that TGA and TAA were associated with a higher risk of OA, and that TAG conferred a lower risk of knee OA in the combined population. Conclusions: Our study suggests that the FN-1 rs940739A/T polymorphism may be an important risk factor of genetic susceptibility to knee OA in the Han Chinese population.

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KW - Single nucleotide polymorphism

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