Association of APOE Genotypes and Total Apolipoprotein E Levels With Galectin-3 and Cardiovascular Risk in Rheumatoid Arthritis Patients

Abstract

Rheumatoid arthritis (RA) defined as a chronic inflammatory disease characterized by painull inflammation of small joints additionally to cardiac disease, probably due to shared pathophysiological pathways and dyslipidemia. The main goal of the presented study is to evaluate the role of the ApoE polymorphisms in Iraqi RA patients and their association with lipid profiles, total ApoE levels, and disease severity markers, including galectin-3 and anti-CCP. A case-control study included 90 RA patients and 90 gender- and healthy controls aged 21 to 70 years with BMI ranging from 18 to 27 kg/m². Fasting serum lipid profiles were analyzed colorimetrically. Total ApoE, ApoE isoforms, anti-CCP, and galectin-3 were quantified by ELISA. Genomic DNA was used to perform ApoE genotyping for the ε2, ε3, and ε4 alleles. RA patients had significantly lower total ApoE levels and markedly higher levels of total cholesterol, LDL, galectin-3, and anti-CCP than controls (P<0.001). The ApoE ε2 allele correlated with reduced cholesterol and LDL-c levels and higher total ApoE levels. In contrast, the ApoE ε4 allele was associated with more severe dyslipidemia, including higher cholesterol and LDL-c levels, as well as increased inflammatory markers, including galectin-3 and anti-CCP, compared with carriers of either ε2 or ε3. ApoE polymorphisms, specifically the ε4 allele, together with elevated galectin-3 levels, are associated with exacerbated dyslipidemia and systemic inflammation in RA, suggesting their potential utility as combined biomarkers for identifying patients with a heightened atherogenic profile who may warrant cardiovascular risk assessment.