Dynamic interaction of obesity, age, MCP-1 Level, and ACE-1 gene with the severity of knee osteoarthritis: a cross-sectional study

M Nasser Mustari; Muh Nasrum Massi; Muhammad A Usman; Achmad Fikry; Agussalim Bukhari; Irfan Idris; Andi A Zainuddin; Endy Adnan; Syakib Bakri; Mizwar Hatta

doi:10.1097/MS9.0000000000000973

Dynamic interaction of obesity, age, MCP-1 Level, and ACE-1 gene with the severity of knee osteoarthritis: a cross-sectional study

Ann Med Surg (Lond). 2023 Jun 20;85(8):3845-3851. doi: 10.1097/MS9.0000000000000973. eCollection 2023 Aug.

Authors

Affiliations

¹ Department of Surgery.
² Departement of Microbiology.
³ Department of Orthopedic and Traumatology.
⁴ Department of Internal Medicine.
⁵ Department of Clinical Nutrition.
⁶ Department of Physiology.
⁷ Department of Public Health and Community Medicine Science, Faculty of Medicine, Hasanuddin University.
⁸ Prodia Clinical Laboratory, Makassar, Indonesia.

Abstract

The risk factors most strongly associated with knee osteoarthritis (OA) are old age and obesity. However, few studies have evaluated the interaction between aging and obesity in conjunction with inflammatory markers and knee OA severity as part of a complete assessment of knee OA management. Therefore, this study aims to evaluate the interaction between obesity, age, inflammation [including the I/D polymorphism of angiotensin converting enzyme-1 (ACE-1)], and the severity of knee OA.

Methods: A total of 80 knee OA patients were included in this cross-sectional study. The severity of knee OA was determined based on the Kellgren-Lawrence system. All patients underwent physical and radiological examination; monocyte chemoattractant protein 1 (MCP-1) markers were measured. The parameters of the ACE-1 gene were examined with sequencing DNA.

Results: There was a significant relationship between age and severity of knee OA (P=0.007), with subjects aged greater than or equal to 65 having a 3.56-fold higher risk of developing moderate to severe OA than subjects aged less than 65. There was a significant difference between body weight and knee OA severity (P=0.026), in which subjects weighing greater than or equal to 60 kg had 3.14 times the risk of experiencing severe knee OA. Multivariate regression analysis indicated that age was the strongest independent variable for knee OA severity compared with body weight. MCP-1 levels were significantly higher in mild knee OA than in moderate to severe knee OA. The DD genotype of the ACE-1 gene increases the risk of severe knee OA by four times in subjects aged greater than or equal to 65 compared to subjects aged less than 65. However, the DD genotype of the ACE-1 gene does not increase the risk of severe knee OA in subjects weighing greater than or equal to 60 kg.

Conclusion: While obesity and age were found to be associated with the severity of knee OA, age emerged as the independent risk factor for knee OA severity. Furthermore, MCP-1 levels were significantly higher in cases of mild knee OA compared to severe knee OA. It was observed that the DD genotype of the ACE-1 gene increases the risk of severe knee OA in individuals aged 65 years or older.

Keywords: ACE-1 gene; age; cross-sectional study; inflammation; knee osteoarthritis; obesity.