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To quantify the expression level of three lncRNAs which are known to be relevant to atherosclerosis (ANRIL, NOS3-AS, and APOA1-AS) in SLE patients and to assess their relationship with atherogenic and inflammatory biomarkers. The circulating levels of these lncRNAs were assessed using RT-PCR, in addition to measurement of E-selectin, V-CAM1, oxidized low-density lipoprotein (oxLDL), total nitric oxide (NOx), and lipid profile in 65 SLE patients (35 atherosclerotic and 30 non-atherosclerotic) and 35 healthy subjects. The expression levels of these lncRNAs were higher in SLE patients than in healthy controls. Importantly, a higher overexpression of these lncRNAs was noticed in atherosclerotic SLE patients than in non-atherosclerotic ones. In atherosclerotic SLE patients, level of ANRIL was positively associated with menopause, SLE duration, SLEDAI, and SLICC and negatively correlated with C3. Moreover, NOS3-AS expression was negatively correlated with total NOx level and HDL, while it was positively correlated with TC, LDL-C, hypertension, metabolic syndrome, obesity and dyslipidemia, CIMT, VCAM-1, E-selectin, oxLDL, SLEDAI, and SLICC. With respect to APOA1-AS, its expression was negatively correlated with HDL-C, whereas it was positively correlated with TC, LDL-C, hypertension, dyslipidemia, obesity, metabolic syndrome, menopause, CIMT, RI, V-CAM1, E-selectin, oxLDL, and SLICC. ANRIL, NOS3-AS, and APOA1-AS could be used as predictive biomarkers for atherosclerosis in SLE. Multivariate analyses identified these lncRNAs as independent predictors for atherosclerosis in SLE. These lncRNAs play a pivotal role in development of atherosclerosis via their significant repercussions atherogenic and inflammatory indices.

Backgroundβ-thalasemia major (β-TM) patients often suffer from various vascular complications together with increased oxidative stress. Hyperhomocysteinemia (Hhcy) has been defined as a risk factor for these complications. Genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to cause Hhcy particularly in individuals with low B-vitamins. However, the status of homocysteine (hcy) in β-TM has not yet been adequately defined.AimTo evaluate the genetic polymorphism of MTHFR C677T among β-TM patients and its prospective contribution to Hhcy and related oxidative changes.Subjects and MethodsGenotyping for MTHFR C677T was done by PCR-RFLP technique. Plasma hcy, vitamin B12, folate, malondialdehyde (MDA), total antioxidant capacity (TAC), oxidized low density lipoprotein (oxLDL), total nitric oxide (NOx) and lipid profile were determined in 66 β-TM patients and 66 control subjects of matched age and sex.ResultsThe prevalence of MTHFR 677TT genotype was significant among β-TM patients (12%) compared to (3%) controls (OR = 4.9, 95%CI:1.2–24.2,P = 0.03). A strong association between Hhcy and MTHFR TT genotype was observed (OR = 7.7, 95%CI:2.8–20.9) where all β-TM patients with TT genotype were hyperhomocystienemic (≥ 15 μmol/l) and having sub-optimal folate level than those with CT or CC genotypes. Hyperhomocystienemic patients have suffered from increased oxidative stress characterized by significant increase in plasma MDA and oxLDL, and a significant reduction of plasma TAC and total NOx. Lipid profile of those patients was severely affected indicated by reduction in HDL and HDL/LDL and elevation in atherogenic index as compared with CC genotype. Other measured parameters were not significantly different among β-TM patients with different MTHFR genotypes.ConclusionThis study suggests that Egyptian β-TM patients with MTHFR 677TT genotype could be at increasing risk of developing Hhcy particularly with folate deficiency. This state of Hhcy may account potentially for most oxidative changes and atherogenic vascular complications frequently reported in β-TM patients.

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