RESUMEN
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.
RESUMEN
BACKGROUND: A number of studies were carried out to assess the association of angiotensin I converting enzyme (ACE) I/D and plasminogen activator inhibitor-1 (PAI-1-1) 4G/5G polymorphisms with susceptibility to type 2 diabetes mellitus (T2DM). However, there are a few studies in Iranian patients with T2DM. Here, we tested for an association of ACE I/D and PAI-1 4G/5G polymorphisms with T2DM risk. METHODS: One hundred-eighteen patients with T2DM and 125 healthy subjects were participates in this study. The ACE I/D (rs4340) and PAI-1 4G/5G (rs1799889) polymorphisms was genotyped by conventional and PCR-RFLP assays, receptively. The associations was evaluated by calculating the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: The genotype distribution of ACE I/D and PAI-1 4G/5G polymorphisms were not deviated from the Hardy-Weinberg equilibrium in healthy controls. The ACE II, ID, and DD genotype frequencies were 18.6%, 48.3%, and 33.1% in the T2DM patients versus 24.0%, 45.6% and 30.4% in healthy subjects, respectively. The PAI-1 4G/4G, 4G/5G, and 5G/5G genotype frequencies were 16.9%, 51.7%, and 31.4% in cases versus 24.8%, 57.6% and 17.6% in controls, respectively. There is a significant distribution in genotype/allele of PAI-1 4G/4G between cases with T2DM and healthy control, but not for ACE I/D. Moreover, the 5G/5G genotype is significantly (OR = 2.139, CI 95% 1.171-3.907, p = 0.013) increased the risk of T2DM by two folds in the cases than healthy controls. CONCLUSIONS: Our findings suggest that PAI-1 4G/5G may be likelihood risk factor for the development of T2DM in the Iranian patients. The higher frequency of PAI-1 5G/5G genotype in patients with T2DM revealed that individuals with the 5G allele may be at higher risk of T2DM development than those with 4G. However, there was no significant association between ACE I/D polymorphism and T2DM in our population. Future rigorous, well-designed studies with larger sample should replicate this study to confirm our findings in Iranian T2DM patients.
