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

Abstract

Osteoarthritis (OA) arises from a intricate interplay of genetic and environmental factors. Numerous studies have explored the link between the growth differentiation factor 5 (GDF-5) +104T>C polymorphism and OA risk, but the findings have been inconclusive. We carried out a case-control study with 704 OA cases and 418 healthy controls. Furthermore, we conducted a meta-analysis by thoroughly searching the literature for relevant studies published until 1 September, 2023. The combined odds ratio and 95% confidence intervals were used to assess the correlation’s strength. A total of 47 independent case-control studies, including 17,602 OA cases and 30,947 controls, were analyzed. Of these, 31 studies (11,176 cases, 16,724 controls) focused on knee OA, 8 studies (3,973 cases, 8,055 controls) examined hip OA, and 6 studies (2244 cases, 5965 controls) investigated hand OA. Overall, our findings suggest that the GDF-5 + 104T>C polymorphism has a protectibe role in development of OA in global scale. Subgroup analyses by ethnicity indicated that this genetic variation provides protection against OA in Caucasian, Asian, and African populations. Further subgroup analysis based on the type of OA showed a decreased risk of knee and hand OA associated with this variation, but not for hip OA. Our combined data indicates that the GDF-5 + 104T>C polymorphism offers protection against the development of OA in general, as well as knee and hand OA. Nevertheless, there was no correlation found between this polymorphism and the development of hip OA.

Keywords:

• Osteoarthritis
• knee
• hip
• hand
• growth differentiation factor 5
• Meta-Analysis

Acknowledgments

The authors wish to express their sincere gratitude to all the study participants who made a valuable contribution to this research.

Authors’ contributions

Conceptualization: Kamran Alijanpour, Seyed Alireza Dastgheib

Data curation: Leila Azizi, Kazem Aghili

Formal analysis: Seyed Alireza Dastgheib, Hossein Neamatzadeh

Investigation: Leila Azizi, Zinatalsadat Dehghani-Manshadi, Somaye Miri

Methodology: Seyed Alireza Dastgheib, Maryam Aghasipour

Supervision: Kamran Alijanpour, Mohammad Bahrami

Validation: Leila Azizi, Seyed Alireza Dastgheib

Writing-original draft: Amirmasoud Shiri, Kazem Aghili, Sahel Khajehnoori

Writing-review, editing and Revision: Amirmasoud Shiri, Zinatalsadat Dehghani-Manshadi

Disclosure statement

The authors confirm no conflict of interest with any financial institution regarding the content discussed in the manuscript.

Additional information

Funding

We conducted this research independently and did not receive any financial assistance or support from any organization or institution.