Association between angiotensin-converting enzyme (ACE) gene I/D polymorphism with the risk of knee OA: A systematic review, meta-analysis, and meta-regression.

Syakib Bakri, Agussalim Bukhari, Haerani Rasyid, M Nasser Mustari, Muh Nasrum Massi, Muh Andry Usman, Irfan Idris, Alfian Zainuddin, Endy Adnan, Mizwar Hatta, Achmad Fikry, Audrey Suryani Soetjipto

Journal: F1000Research 2024;13():146

PMID: 38779312

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Abstract

BACKGROUND

Previous studies have linked genetics to knee osteoarthritis. Angiotensin-converting enzyme (ACE) gene I/D polymorphism may cause OA. However, evidence remains inconsistent. This study examines knee OA risk and ACE gene I/D polymorphism.

METHODS

We explored Europe PMC, Medline, Scopus, and Cochrane Library using keywords. Three assessment bias factors were assessed using the Newcastle-Ottawa Scale (NOS). Criteria for inclusion: (1) Split the study population into knee OA patients and healthy controls; (2) Analysed the ACE gene I/D polymorphism; (3) Case-control or cross-sectional surveys. Studies with non-knee OA, incomplete data, and no full-text were excluded. The odds ratio (OR) and 95% confidence intervals (95% CI) were calculated using random-effect models.

RESULTS

A total of 6 case-control studies consist of 1,226 patients with knee OA and 1,145 healthy subjects as controls were included. Our pooled analysis revealed that a significant association between ACE gene I/D polymorphism and risk of knee OA was only seen in the dominant (DD + ID vs. II) [OR 1.69 (95% CI 1.14 - 2.50), p = 0.009, I2 = 72%], and ID vs. II [OR 1.37 (95% CI 1.01- 1.86), p = 0.04, I2 = 43%] genotype models. Other genotype models, including recessive (DD vs. ID + II), alleles (D vs. I), DD vs. ID, and DD vs. II models did not show a significant association with knee OA risk. Further regression analysis revealed that ethnicity and sex may influence those relationships in several genotype models.

CONCLUSIONS

Dominant and ID vs. II ACE gene I/D polymorphism models increased knee OA risk significantly. More research with larger samples and different ethnic groups is needed to confirm our findings. After ethnicity subgroup analysis, some genetic models in our study showed significant heterogeneities, and most studies are from Asian countries with Asian populations, with little evidence on Arabs.

Address: Division of Orthopaedic and Traumatology, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia.; Department of Clinical Microbiology, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia.; Division of Orthopaedic and Traumatology, Department of Orthopaedic and Traumatology,, Hasanuddin University, Makassar, South Sulawesi, Indonesia.; Department of Clinical Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia.; Department of Physiology, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia.; Department of Public Health, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia.; Division of Rheumatology, Department of Internal Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia.; Division of Kidney and Hypertension, Department of Internal Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia.; Specialty & Research Laboratory, The Prodia Education and Research Institute, Jakarta City, Jakarta, Indonesia.; Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia.

DOI: 10.12688/f1000research.140233.1

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MeSH Terms: Humans, Case-Control Studies, Genetic Association Studies, Genetic Predisposition to Disease, INDEL Mutation, Osteoarthritis, Knee, Peptidyl-Dipeptidase A, Polymorphism, Genetic, Risk Factors