ATXN2 and its neighbouring gene SH2B3 are associated with increased ALS risk in the Turkish population

Expansions of the polyglutamine (polyQ) domain (≥34) in Ataxin-2 (ATXN2) are the primary cause of spinocerebellar ataxia type 2 (SCA2). Recent studies reported that intermediate-length (27–33) expansions increase the risk of Amyotrophic Lateral Sclerosis (ALS) in 1–4% of cases in diverse populations. This study investigates the Turkish population with respect to ALS risk, genotyping 158 sporadic, 78 familial patients and 420 neurologically healthy controls. We re-assessed the effect of ATXN2 expansions and extended the analysis for the first time to cover the ATXN2 locus with 18 Single Nucleotide Polymorphisms (SNPs) and their haplotypes. In accordance with other studies, our results confirmed that 31–32 polyQ repeats in the ATXN2 gene are associated with risk of developing ALS in 1.7% of the Turkish ALS cohort (p = 0.0172). Additionally, a significant association of a 136 kb haplotype block across the ATXN2 and SH2B3 genes was found in 19.4% of a subset of our ALS cohort and in 10.1% of the controls (p = 0.0057, OR: 2.23). ATXN2 and SH2B3 encode proteins that both interact with growth receptor tyrosine kinases. Our novel observations suggest that genotyping of SNPs at this locus may be useful for the study of ALS risk in a high percentage of individuals and that ATXN2 and SH2B3 variants may interact in modulating the disease pathway

Evaluation of common carotid artery in type 1 diabetes mellitus patients through speckle tracking carotid strain ultrasonography

PURPOSEWe aimed to evaluate the effectiveness of speckle tracking carotid strain (STCS) technique, which enables measurement of arterial stiffness and strain parameters, in the detection of early atherosclerotic findings in type 1 diabetes mellitus (T1DM).METHODSWe prospectively enrolled 30 T1DM patients and 30 age- and sex-matched control participants with no history of cardiovascular disease. All study population underwent carotid ultrasonography. Radial and circumferential movement of the common carotid artery (CCA) in the transverse plane as the well as the radial movement of the CCA in the longitudinal plane were calculated automatically by using the STCS method. In addition, the strain (%), strain rate (per second), and peak circumferential and radial displacements (mm) were calculated. Arterial stiffness parameters, such as elastic modulus, distensibility, arterial compliance, and β-stiffness index, were calculated using the radial measurements. The mean value of the carotid intima media thickness (CIMT) was calculated semi-automatically for each CCA, in the longitudinal plane. We also analyzed the patients’ overall body composition.RESULTST1DM and control groups were compared in terms of strain and stiffness parameters and no statistically significant difference was found (p > 0.05). CIMT was higher in diabetic patients than in the control group (p = 0.039). In both groups, age was correlated with all arterial stiffness and strain parameters (p < 0.05). The duration of diabetes was also correlated with β-stiffness index, distensibility, and elastic modulus in the longitudinal plane (p < 0.05). In the diabetic group, abdominal fat ratio, whole body fat ratio, and fat mass were correlated with radial and circumferential displacement and strain parameters in transverse plane, and radial displacement in longitudinal plane (p < 0.05, for each). Diabetic patients were divided into subgroups according to the presence of nephropathy and dyslipidemia. Although no significant difference was found between the groups in terms of CIMT, patients with nephropathy had higher values for transverse and longitudinal elastic modulus, pulse-wave velocity, and longitudinal β-stiffness index, as well as lower values for longitudinal arterial compliance and distensibility, compared with patients without nephropathy (p < 0.05). Also, patients with dyslipidemia had higher longitudinal β-stiffness and elastic modulus values compared with patients without dyslipidemia (p < 0.05).CONCLUSIONSTCS ultrasonography is an effective, easy, and noninvasive method for evaluating the arterial elasticity. It may provide an early assessment of atherosclerosis in patients with T1DM, especially in the presence of nephropathy and dyslipidemia; thus, together with CIMT measurement, it may be used more frequently to detect subclinical damage and stratify atherosclerosis