Contribution of MTHFR gene variants in lupus related subclinical atherosclerosis

Giannelou, Maira; Nezos, Adrianos; Fragkioudaki, Sofia; Kasara, Dimitra; Maselou, Kyriaki; Drakoulis, Nikolaos; Ioakeimidis, Dimitrios; Moutsopoulos, Haralampos Μ.; Mavragani, Clio P.

doi:10.1016/j.clim.2018.02.014

Cited by 28 publications

(40 citation statements)

References 47 publications

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“…In a meta-analysis of 46 genome-wide association studies a signi cant association between the homozygous TT allele of GCKR rs1260326 and higher circulating TG levels was observed (40) although the atherogenic effect of this variant is controversial (41)(42)(43). The evaluation of non-traditional cardiovascular risk factors revealed statistically signi cant differences in plasma homocysteine concentrations in patients with carotid plaque (p=0.037) which is consistent with the reported role of homocysteine as a potential contributor to the increased burden of atherosclerotic disease in SLE (44,45). Antiphospholipid antibodies and SLE nephritis are tightly related to the risk of cardiovascular events in SLE patients (24,26,46), although neither antiphospholipid syndrome nor lupus nephritis or the complement were statistically relevant in our population.…”

Section: Discussionsupporting

confidence: 66%

Asymptomatic Carotid Atherosclerosis Cardiovascular Risk Factors and Common Hypertriglyceridemia Genetic Variants in Patients with Systemic Erythematosus Lupus

Fanlo-Maresma

Candás-Estébanez

Esteve-Luque

et al. 2020

Preprint

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Background and aims: SLE is a systemic autoimmune disease associated with an increased cardiovascular risk which is related with the characteristic dyslipidemia of SLE. This consists of an alteration of triglyceride-rich lipoprotein metabolism and an increased concentration of apoB containing particles. The objective of this study is to know the prevalence of carotid atherosclerosis and to analyze its relationship with dyslipidemia and its related genetic factors in a population of SLE patients.Methods: Seventy-one SLE female were recruited. A carotid ultrasound was performed to evaluate the presence of atheromatous plaques and cIMT. Lipid profile and analysis of ZPR1, APOA5 and GCKR genes were carried out. SLE patients were analyzed according to the presence or absence of carotid plaques. Statistical analyses were performed to evaluate the relationship between lipid parameters and these allelic variants involved in triglyceride metabolism.Results: SLE patients with carotid plaque had higher concentrations of plasma triglyceride than SLE patients without carotid plaque (1.5 vs 0.9 mmol/L, respectively, p=0.001), Non-HDLC (3.5 vs 3.1 mmol/L, p= 0.025) and apoB (1.0 vs 0.9 g/L, p=0.010). GCKR (c.1337C>T) C-allele was observed in 83.3% and 16.7% (p=0.047) of patients with and without carotid plaque, respectively. The GCKR (c.1337C>T) CC genotype (OR= 0.03; [95% CI] [0.002 to 0.53], p=0.016), and triglyceride concentrations (OR= 7.57; [95% CI] [1.43 to 40.19], p=0.017) were independently associated with the diagnosis of carotid plaque.Conclusions: plasma triglyceride concentration and CGKR CC homozygosity for CGKR gene are independent predictive factors of carotid atherosclerosis in women with systemic lupus erythematosus.Keywords: triglycerides, CGKR gene, Non-HDLC, atherosclerosis, systemic lupus erythematosus.

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Section: Discussionsupporting

confidence: 66%

Asymptomatic Carotid Atherosclerosis Cardiovascular Risk Factors and Common Hypertriglyceridemia Genetic Variants in Patients with Systemic Erythematosus Lupus

Fanlo-Maresma

Candás-Estébanez

Esteve-Luque

et al. 2020

Preprint

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“…Demographic data (age, sex and body mass index (BMI)), clinical and laboratory features, disease activity/damage scores (SLEDAI: Systemic Lupus Erythematosus Disease Activity Index, SLICC: Systemic Lupus International Collaborating Clinics), current and prior medications, traditional risk factors for atherosclerosis and osteoporosis and bone metabolism parameters were thoroughly recorded as previously described. 29 30 Additionally, all patients underwent evaluation for traditional CVD risk factors such as serum cholesterol, triglyceride and homocysteine levels as well as bone metabolism markers including PTH and 25-OHD serum levels. Blood was drawn in the morning in fasting conditions.…”

Section: Methodsmentioning

confidence: 99%

Atherosclerosis in SLE: a potential role for serum parathormone levels

Giannelou

Skarlis

Stamouli³

et al. 2020

Lupus Sci Med

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ObjectiveA link between bone metabolism and cardiovascular (CV) disease has been suggested mainly in the general population. In the current study we explored whether altered bone metabolism influence CV risk in patients with SLE.MethodsIn 138 consecutive patients with SLE, atherosclerosis was assessed by the presence of plaque and/or arterial wall thickening in carotid/femoral arteries by ultrasound. Bone mineral density (BMD) levels and hip/spinal cord fractures together with classical CV disease and osteoporosis risk factors including serum 25(OH) vitamin D3 and parathormone (PTH) levels were recorded in all patients. Serum osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand were quantitated by commercial ELISA. Statistical analysis included both univariate and multivariate models.ResultsAbnormal PTH serum concentrations (>65 pg/mL)—but not 25(OH) vitamin D3 serum levels—were identified as a risk factor for both plaque formation and arterial wall thickening in patients with SLE (ORs (95% CIs): 8.2 (1.8 to 37.4) and 3.9 (1.3 to 11.8), respectively). This association remained significant following adjustment for vitamin D3 levels and classical CV risk factors. Moreover, an independent association between osteoporosis with plaque formation and arterial wall thickening was detected following adjustment for total steroid dose, premature menopause and disease duration (ORs (95% CIs): 5.3 (1.1 to 26.2) and 3.5 (1.1 to 11.4), respectively). An inverse correlation between femoral neck BMD values and intima–medial thickness scores was also observed (r: −0.42, p=0.008).ConclusionsThese findings further strengthen the concept of shared pathophysiological mechanisms between atherogenesis and altered bone metabolism in autoimmune populations, revealing heightened PTH levels as a potential marker for atherosclerosis among patients with SLE.

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“…CV events are the leading cause of morbidity and mortality in SLE and prevention of progression of atherosclerosis to clinically manifest atherosclerosis is an important task. Genetic factors, traditional risk factors such as smoking, hypertension, hyperlipidaemia, diabetes mellitus and obesity, and disease factors, for example, SLE-related immune activity, accumulated disease damage and treatments contribute to vessel changes and accelerated atherosclerosis in SLE 8–13. It is unclear whether contribution of classical CV risk factors and inflammatory factors to vascular changes is different in patients with SLE in comparison with the general population.…”

Section: Introductionmentioning

confidence: 99%

Similar progression of carotid intima–media thickness in 7-year surveillance of patients with mild SLE and controls, but this progression is still promoted by dyslipidaemia, lower HDL levels, hypertension, history of lupus nephritis and a higher prednisolone usage in patients

et al. 2020

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ObjectiveTo compare progression of subclinical atherosclerosis and factors promoting it in patients with SLE and controls.MethodsConsecutive patients with SLE and age-matched, sex-matched population controls from the SLEVIC cohort were assessed at inclusion and after 7 years with standardised data collection and carotid ultrasound. Effect of risk factors on carotid intima–media thickness (cIMT) progression was examined with adjusted linear mixed models.ResultsA total of 77 patients and 74 controls, 68% and 61% of the original cohort, completed follow-up. The patients were (mean) 47 years old, 90% were women, and controls were 51 years old, 92% women. Patients had disease duration of (mean) 11 years, mild disease activity and low severity at both assessments. Baseline cIMT did not differ between the groups. An average absolute cIMT progression was 0.009 mm/year in patients and 0.011 mm/year in controls, intergroup difference p=0.9.Of factors at inclusion, dyslipidaemia, lower levels of high-density lipoprotein (HDL) and carotid plaque in patients and controls, and higher systolic blood pressure, total cholesterol:HDL and LDL:HDL ratios and triglycerides in patients were associated with cIMT progression. Of factors at follow-up, hypertension and blood lipids in patients and HDL in controls were significantly associated with cIMT progression. History of lupus nephritis and a higher average dose of prednisolone used since diagnosis were associated with cIMT progression in patients. Associations of risk factors with cIMT progression were stronger in presence of plaques.ConclusionWe observed a statistically comparable progression of cIMT in patients with mild SLE and controls over 7 years, which implies that progression of subclinical atherosclerosis in some patients with SLE could follow that of the general population. Traditional cardiovascular (CV) risk factors, history of lupus nephritis and higher use of corticosteroids promote cIMT progression in SLE. Detection of carotid plaque may add to CV risk stratification.

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Contribution of MTHFR gene variants in lupus related subclinical atherosclerosis

Cited by 28 publications

References 47 publications

Asymptomatic Carotid Atherosclerosis Cardiovascular Risk Factors and Common Hypertriglyceridemia Genetic Variants in Patients with Systemic Erythematosus Lupus

Asymptomatic Carotid Atherosclerosis Cardiovascular Risk Factors and Common Hypertriglyceridemia Genetic Variants in Patients with Systemic Erythematosus Lupus

Atherosclerosis in SLE: a potential role for serum parathormone levels

Similar progression of carotid intima–media thickness in 7-year surveillance of patients with mild SLE and controls, but this progression is still promoted by dyslipidaemia, lower HDL levels, hypertension, history of lupus nephritis and a higher prednisolone usage in patients

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