Image_1_The alteration of left ventricular strain in later-onset spinal muscular atrophy children.tif

BackgroundPatients with spinal muscular atrophy (SMA) may suffer from multisystem injury, including an impaired cardiovascular system. However, M-mode echocardiography, the current dominant echocardiographic modality, is limited in the detection of myocardial injury. We considered the use of left ventricular strain imaging in detecting myocardial injury and explored the serum lipid profile related to cardiovascular disease in later-onset SMA children.MethodsA case-control study involving 80 patients with later-onset SMA and 80 age-, gender-, and body surface area-matched control children was conducted in a single tertiary pediatric hospital in China. Data on the left ventricular strain measured using two-dimensional speckle tracking echocardiography, left ventricular function parameters assessed by M-mode echocardiography, and serum lipid profile of these two groups were retrospectively collected for differential analysis.ResultsThe mean age of the 80 SMA patients were (6.87 ± 2.87) years, of which 46 were type 2 and 34 were type 3 patients. The global longitudinal strain (GLS) of the SMA group (−18.7 ± 2.9%, p ConclusionCompared with healthy controls, later-onset SMA children presented with reduced GLS and prolonged TTPLS while the LVEF and LVFS values were within normal range. In particular, whether a reduced GLS or prolonged TTPLS in later-onset SMA compared to the control group can predict the risk of future cardiomyopathy remains to be investigated.</p

Five SNPs in the genomic region of <i>PVRL2-TOMM40-APOE</i> locus.

<p><b>A</b>. Genomic region of <i>PVRL2-TOMM40-APOE</i> locus associated with human longevity, horizontal arrows indicate the transcriptional orientations of individual genes. <b>B</b>. Pairwise LD among five SNPs in and surrounding the <i>TOMM40</i> gene in the replication study. The LD spans the region including the <i>PVRL2, TOMM40</i> and <i>APOE</i>, a distance of 45 kb. Linkage disequilibrium was measured by the D′ statistic using the data from all subjects. A D′ value of 100 indicates a complete LD between 2 markers, and a D′ value of 0 indicates a complete linkage equilibrium. Haploview version 4.2 software was used for the analysis.</p

Replication study for the association of the associated SNPs in a replication cohort.

a<p>Genomic positions are according to NCBI build 36;</p>b<p>Minor allele/major allele;</p>c<p>The genotype counts are presented as homozygote/heterozygote/wildtype;</p>d<p>Allelic <i>P</i> value has been adjusted for sex;</p>e<p>Data from different study cohorts (initial cohort and replication cohort) were combined using Mantel-Haenszel models with fixed effects;</p>f<p>P values after multiple correction (combined P*5).</p

Genotype Analysis of 5 SNPs by recessive and dominant models.

<p>*<i>P_rec</i>, the <i>P</i> value of recessive model, <i>P_dom</i>, the P value of dominant model;</p><p>**OR, the odds ratio of homozygote; CI, Confidence Interval.</p

Samples used for analysis.

<p>*The age when the cases and controls were recruited. ±: standard deviation;</p

Conditional analysis of the <i>PVRL2-TOMM40-APOE</i> locus in a replication cohort.

a<p>Genomic positions are according to NCBI build 36;</p>b<p>Minor allele/major allele;</p>c<p>The results of association testing of the <i>PVRL2-TOMM40-APOE</i> locus when the allelic dosage of rs519825, rs2075650 or rs405509 was included in the regression model.</p

Extensive study for the association of SNPs in the vicinity of <i>TOMM40-APOE</i> region.

a<p>Genomic positions are according to NCBI build 36;</p>b<p>Minor allele/major allele;</p>c<p>The genotype counts are presented as homozygote/heterozygote/wildtype;</p