Τίτλος:
Contribution of MTHFR gene variants in lupus related subclinical atherosclerosis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objective: Elevated concentrations of homocysteine have been previously identified as an independent risk factor for subclinical atherosclerosis in patients with systemic lupus erythematosus (SLE). Given that heightened homocysteine levels are known to be strongly influenced by genetic factors, in the current study we investigated the contribution of high homocysteine levels as well as of functional polymorphisms of the gene encoding for the enzyme 5, 10- methylenetetrahydrofolate reductase (MTHFR) to atherosclerotic disease characterizing SLE patients. Methods: Peripheral DNA samples from 150 SLE patients, 214 rheumatoid arthritis (RA) patients and 561 age/sex matched apparently healthy volunteers (HC) were genotyped by PCR-based assays for the detection of the MTHFR gene polymorphisms (c. 677C > T and c. 1298A > C). All SLE patients and 30 age sex matched RA patients underwent assessment for subclinical atherosclerosis [ultrasound measurement of intima-media thickness scores (IMT) and detection of carotid and/or femoral (C/F) plaque] and complete clinical and laboratory evaluation including serum homocysteine levels. Data were analyzed using univariate and multivariate models (SPSS 21.0). Results: Hyperhomocysteinemia was detected in 26.0% of SLE patients compared to 6.7% of age/sex matched RA controls (p = 0.02). Higher serum B12 levels and decreased frequency of the MTHFR 677TT variant in RA patients could potentially account for the observed differences between the groups. In SLE patients, both hyperhomocysteinemia and MTHFR 677TT genotype were identified as independent contributors for plaque formation, following adjustment for traditional cardiovascular risk factors and disease related features, including age, sex, BMI, cholesterol and triglyceride levels, presence of arterial hypertension, smoking (pack/years), disease duration and total steroid dose [OR 95% (CI): 5.8 (1.0–35.8) and 5.2 (1.1–24.0), respectively]. MTHFR 677TT genotype, but not hyperhomocysteinemia was also found to confer increased risk for arterial wall thickening, after the above confounders were taken into account [OR (95%) CI: 4.9 (1.2–20.6)]. Conclusions: Hyperhomocysteinemia and MTHFR 677TT genetic variant emerged as independent risk factors for subclinical atherosclerosis in SLE patients, implying genetic influences as potential contributors to the increased burden of atherosclerotic disease characterizing SLE. © 2018 Elsevier Inc.
Συγγραφείς:
Giannelou, M.
Nezos, A.
Fragkioudaki, S.
Kasara, D.
Maselou, K.
Drakoulis, N.
Ioakeimidis, D.
Moutsopoulos, H.M.
Mavragani, C.P.
Περιοδικό:
Clinical Immunology Newsletter
Εκδότης:
Academic Press Inc.
Λέξεις-κλειδιά:
5,10 methylenetetrahydrofolate reductase (FADH2); cholesterol; creatinine; cyanocobalamin; DNA; genomic DNA; homocysteine; steroid; triacylglycerol; methylenetetrahydrofolate reductase (NADPH2); MTHFR protein, human, adult; amino acid blood level; arterial wall thickening; arterial wall thickness; Article; atherosclerosis; body mass; cardiovascular risk; carotid atherosclerosis; cholesterol blood level; clinical feature; comparative study; controlled study; creatinine blood level; disease duration; echography; female; femoral artery; genetic association; genetic variability; genotype; human; hyperhomocysteinemia; hypertension; major clinical study; male; middle aged; molecular pathology; patient; polymerase chain reaction; priority journal; rheumatoid arthritis; single nucleotide polymorphism; smoking; subclinical atherosclerosis; systemic lupus erythematosus; triacylglycerol blood level; vitamin blood level; atherosclerosis; gene frequency; genetic association study; genetic polymorphism; genetic predisposition; genetics; genotype; Greece; prognosis; risk; systemic lupus erythematosus, Adult; Atherosclerosis; Carotid Intima-Media Thickness; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Greece; Humans; Hyperhomocysteinemia; Lupus Erythematosus, Systemic; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic; Prognosis; Risk
DOI:
10.1016/j.clim.2018.02.014
