Does Down's syndrome support the homocysteine theory of atherogenesis? Experience in elderly subjects with trisomy 21

Down syndrome (DS) is generally considered as an "atheroma-free model". In this preliminary study, we investigated homocysteine, folate and Vitamin B(12) levels in 13 DS patients (male, average age 60 years) and 20 age-matched individuals. We also studied lipid fractions, and polymorphisms for Cystothionine beta-synthase (CBS), 5,10-methyl-tetrahydro-folate reductase (MTHFR) and apolipoprotein E (Apo-E) genes. However, DS patients with the MTHFR TT genotype showed an increased of plasma homocysteine (tHcy). Our results indicate that this group of "healthy old" Down syndrome patients, although showing some classical biochemical risk factors for atherosclerosis, did not suffer clinical cardiovascular alterations.     

Susceptibility to Guillain-Barré syndrome is associated to polymorphisms of CD1 genes

Guillain-Barré syndrome (GBS) is the prototype of a postinfectious autoimmune neuropathy. Molecular mimicry between glycolipid antigens expressed by an infective antigen such as Campylobacter jejuni and the human peripheral nerve has been hypothesized to be the causative mechanism of GBS. However, only 1/1000 of C. jejuni enteritis develops GBS. This emphasizes the importance of host-related factors in the development of the disease. HLA studies in GBS failed to show an association or gave conflicting results but MHC class I and II process and present peptides to T lymphocytes making unlikely that the HLA system plays a role in GBS with autoantibodies against self-gangliosides. CD1 molecules are MCH-like glycoproteins specialized in capturing and presenting a variety of glycolipid to antigen-specific T cells. There are five closely linked CD1 genes in humans located in chromosome 1 (named CD1A, B, C, D, and E) all showing limited polymorphism in exon 2 which codifies for the alpha1 domain of CD1 molecules. The nucleotide substitutions in CD1B and CD1C are rare and reported to be silent. In 100 controls and 65 GBS patients (21 with a recent C. jejuni infection and 35 with anti-glycolipid antibodies) we used direct sequencing by polymerase chain reaction to genotype exon 2 of CD1A, CD1D and CD1E genes. CD1D is monomorphic in both controls and patients whereas CD1A and CD1E are biallelic in exon 2. Subjects with CD1E*01/01 genotype are 2.5 times more likely to develop GBS, whereas subjects with CD1A*01/02 or CD1E*01/02 have a reduced relative risk by 3.6 and 2.3 times respectively. The combination of CD1A*01/02 and CD1E*01/02 reduces by 5 times the risk of developing GBS. Although a correlation between CD1E*01/01 genotype and recent C. jejuni infection or presence of antiganglioside antibodies was not found the overall findings indicate that susceptibility to develop GBS is associated with polymorphisms of CD1E and CD1A genes.     

Body composition changes and cardiometabolic benefits of a balanced Italian Mediterranean Diet in obese patients with metabolic syndrome

Metabolic syndrome (MS) is a cluster of metabolic alteration associated with a higher risk of cardiovascular disease and overall mortality than the single alterations alone. The Italian Mediterranean Diet (IMD) can exert a positive effect on cardiovascular risk and related morbidity and mortality. The aim was to evaluate the benefits of dietary intervention based on a typical IMD on body composition, cardiometabolic changes and reduction in cardiovascular disease in patients with MS. Eighty White Italian subjects with MS were prescribed a balanced hypocaloric IMD. We investigated dietary habits and impact of the diet on health status, blood biochemical markers, anthropometric measurements and body composition during a 6-month follow-up period. Body composition, fat mass and distribution were assessed by Dual X-ray absorptiometry. Adherence to the IMD led to a decrease in body weight (102.59 ± 16.82 to 92.39 ± 15.94 kg, p < 0.001), body mass index (BMI) (38.57 ± 6.94 to 35.10 ± 6.76, <0.001) and waist circumference (112.23 ± 12.55 vs 92.42 ± 18.17 cm, p < 0.001). A significant loss of total body fat especially in waist region was observed. The MS was resolved in 52 % of the patients. Significant improvements in systolic and diastolic blood pressure and fasting glucose occurred. Low-density lipoprotein cholesterol was reduced from 128.74 ± 33.18 to 108.76 ± 38.61 mg/dl (p < 0.001), triglycerides from 169.81 ± 80.80 to 131.02 ± 63.88 mg/dl (p < 0.001). The present results suggest that a dietary intervention based on a typical IMD effectively promotes weight loss and reduces the growing burden of cardiovascular risk factors that typifies patients with MS.     

Prediction of carotid plaques in hypertensive patients by risk factors, left ventricular hypertrophy, and epicardial adipose tissue thickness

Hypertension and other risk factors (RFs) predispose to carotid plaques (CPs). An association between left ventricular hypertrophy (LVH) or epicardial adipose tissue (EAT) and CPs has also been reported. The aim of the study was to evaluate whether the assessment of LVH and EAT thickness, beyond RFs, would be of additive value in predicting CPs in hypertensive subjects. We studied 548 hypertensive patients aged ≥50 years without carotid bruit. LVH and CPs were evaluated and defined according to standard criteria. EAT was measured by echocardiography above the free wall of the right ventricle at end diastole. The presence of LVH and EAT thickness above the median value (3.9 mm) together significantly increased prevalence of CPs in subjects with 0–1 risk factor, but not in those with ≥2 RFs who showed high prevalence of CPs independently of LVH and/or EAT. Receiver operating characteristic curve analysis showed that the addition of LVH and higher EAT thickness together significantly improved prediction of CPs in patients with 0–1 risk factor. Indeed, the area under the curve improved from 0.63 (0.56–0.69) to 0.73 (0.67–0.79), which was significantly higher (p < 0.05). In patients with ≥2 RFs, the addition of LVH and EAT did not significantly improve prediction of CPs. This study shows that the presence of LVH and higher EAT thickness together improves prediction of CPs in hypertensive patients with 0–1 risk factor and that those with ≥2 RFs show high prevalence of CPs independently of LVH and/or EAT.     

Pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype: effect of multiple gene interactions

Genetic studies have shown that individuals with certain HLA alleles have a higher risk of specific autoimmune disease than those without these alleles. Particularly, the association in all Caucasian populations of an impressive number of autoimmune diseases with genes from the HLA-B8,DR3 haplotype that is part of the ancestral haplotype (AH) 8.1 HLA-A1, Cw7, B8, TNFAB*a2b3, TNFN*S, C2*C, Bf*s, C4A*Q0, C4B*1, DRB1*0301, DRB3*0101, DQA1*0501, DQB1*0201 has been reported by different research groups. This haplotype, the more common one in northern Europe, is also associated in healthy subjects with a number of immune system dysfunctions. It has been proposed that a small number of genes within the 8.1 AH modify immune responsiveness and hence affect multiple immunopathological diseases. In this paper, the characteristic features of this haplotype that might give rise to these diverse conditions are reviewed, focusing on the role of multiple gene interactions in disease susceptibility of 8.1 AH.