Interaction between angiotensin-converting enzyme gene rs4343 polymorphism, environment factors, and angiotensin II level on susceptibility to knee osteoarthritis.

OBJECTIVES: Osteoarthritis (OA) is a complex multifactorial disease. The association of knee OA risk with ACE gene rs4343 polymorphism, gene environment synergistic effect, and angiotensin II serum level has not been previously examined. Therefore, we investigate the ACE gene rs4343 polymorphism in knee OA, and its association with severity of knee OA, and angiotensin II serum level. METHODS: Using a case-control design, we recruited 200 subjects (100 cases and 100 controls) and all were subjected to genotyping of rs4343 SNP by real-time polymerase chain reaction and assay of serum angiotensin II level by ELISA. RESULTS: G containing genotypes (AG and GG) and G allele frequencies of the ACE rs4343 polymorphism were significantly higher in the case group than that in the control group. There was significant association between ACE rs4343 genotypes and risk of knee OA under the following genetic inheritance models: GG vs. AA (P=0.003), AA vs. GG/AG (P=0.014), AG/AA vs. GG (P=0.037), and G vs. A (P<0.001). Stratified analyses showed ACE rs4343 polymorphism was evidently associated with a significantly increased risk of knee OA among those had BMI≥25% (adjusted OR=3.016; 95% CI 1.052-8.648; P=0.040). Additionally, knee OA patients with GG genotype had greater knee specific WOMAC index, Kellgren score, and serum angiotensin II level than those with AA or GA genotypes. CONCLUSION: The investigated polymorphism in the ACE gene rs4343 may reflect the risk and severity of knee OA in the Egyptian population, particularly with the GG genotype. The interaction between ACE gene rs4343 polymorphism and obesity further increased the risk of knee OA. Moreover, the higher angiotensin II level may be involved in the pathogenesis of knee OA.

Interleukin 6, interleukin 17, disease-related and contextual factor association with depression, and its severity in patients with rheumatoid arthritis.

OBJECTIVE: Depression is very prevalent in rheumatoid arthritis (RA) compared with the general population and may be associated with poor clinical outcomes. Identifying factors associated with depression could improve outcomes for this at risk group. However, few studies have comprehensively examined the association of contextual and disease-related factors as well as pro inflammatory cytokines interleukin 6 (IL-6) and interleukin 17 (IL-17) with depression in RA. Therefore, we aimed to identify the factors significantly associated with depression and severe depression in RA, thus providing a reference for applying clinical care interventions for patients with RA. METHODS: An observational cross-sectional study was conducted on 120 RA patients. Potential determinants included contextual and disease-related factors and laboratory variables. Enzyme-linked immunosorbent assay was used to measure serum IL-6 and IL-17 levels. Depression was assessed using the Arabic version of the Beck Depression Inventory-II questionnaire. RESULTS: A total of 120 patients were included, and up to 67.5% had some degree of depression with 60% having moderate to severe depression. The severity of disease activity of RA (DAS28-ESR (OR, 1.63; 95% CI, 0.899-3.755), HAQ scores (OR, 1.27; 95% CI, 0.702-2.933), and VAS scores for pain (OR, 2.2; 95% CI, 1.251-5.223)), besides elevated serum IL-6 (OR, 1.51; 95% CI, 0.832-3.475), IL-17 (OR, 1.28; 95% CI, 0.706-2.947), and CRP levels (OR, 1.20; 95% CI, 0.923-2.882) were significantly associated with depression and its severity in the multivariate analysis. CONCLUSION: Depression is frequent in RA and is strongly associated to elevated serum IL-6, IL-17, CRP levels, and disease activity-related factors. Key Points • RA patients are at increased risk of developing depression, particularly if their level of disease activity scores, serum IL-6, and IL-17 levels increases. • Patient characteristics associated with depression in RA include living without family, without employments, and with co-morbid hypertension, while RA disease factors are pain, functional disability, and high disease activity. • A multidisciplinary cooperative approach to RA patient care with regular assessments of these factors associated with depression should be incorporated into routine care programs to improve patients' self care capabilities and mitigate or prevent depression in these patients.