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horacic ortic neurysms and issections (TAAD) are a major cause of death in the United States. The spectrum of TAAD ranges from genetic disorders, such as Marfan syndrome, to sporadic isolated disease of unknown cause. We hypothesized that genomic copy number variants (CNVs) contribute causally to early onset TAAD (ETAAD). We conducted a genome-wide SNP array analysis of ETAAD patients of European descent who were enrolled in the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC). Genotyping was performed on the Illumina Omni-Express platform, using PennCNV, Nexus and CNVPartition for CNV detection. ETAAD patients (n = 108, 100% European American, 28% female, average age 20 years, 55% with bicuspid aortic valves) were compared to 7013 dbGAP controls without a history of vascular disease using downsampled Omni 2.5 data. For comparison, 805 sporadic TAAD patients with late onset aortic disease (STAAD cohort) and 192 affected probands from families with at least two affected relatives (FTAAD cohort) from our institution were screened for additional CNVs at these loci with SNP arrays. We identified 47 recurrent CNV regions in the ETAAD, FTAAD and STAAD groups that were absent or extremely rare in controls. Nine rare CNVs that were either very large (>1 Mb) or shared by ETAAD and STAAD or FTAAD patients were also identified. Four rare CNVs involved genes that cause arterial aneurysms when mutated. The largest and most prevalent of the recurrent CNVs were at Xq28 (two duplications and two deletions) and 17q25.1 (three duplications). The percentage of individuals harboring rare CNVs was significantly greater in the ETAAD cohort (32%) than in the FTAAD (23%) or STAAD (17%) cohorts. We identified multiple loci affected by rare CNVs in one-third of ETAAD patients, confirming the genetic heterogeneity of TAAD. Alterations of candidate genes at these loci may contribute to the pathogenesis of TAAD. [ABSTRACT FROM AUTHOR]

Introduction: Peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α) plays an important role in Parkinson's disease (PD). The aim of the study was to evaluate PGC-1α gene expression in the peripheral blood of PD patients. We also investigated PGC-1α-related gene variants and identified whether they are associated with PGC-1α gene expression.Methods: 259 PD patients and 253 healthy controls were included in this study. PPARGC1A (the gene encoding PGC-1α) expression levels were tested using real-time PCR. Single nucleotide polymorphisms (SNPs) of the PGC-1α-related genes (PPARGC1A, PPARG and SIRT1) were genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS).Results: PPARGC1A levels were significantly decreased in PD patients (P = 0.000) and negatively correlated with the patients' H&Y stage (r = -0.212, P = 0.039) and UPDRS-III score (r = -0.208, P = 0.044), after correcting, these correlations disappeared. The genotype frequencies of PGC-1α-related gene variants were not associated with the risk of PD. PPARGC1A rs2970870 variant was associated with the NMS score (P = 0.026), SIRT1 rs7895833 variant was associated with HAMA score (P = 0.029). PPARG rs4684847 variant was associated with MMSE score (P = 0.031). PPARG rs1801282, rs4684847, rs3856806 variants were associated with MoCA score. After correcting, only the association between PPARG rs4684847 and MoCA score remained significant (FDR = 0.048). PGC-1α-related gene variants had no effect on PGC-1α gene expression.Conclusion: The decreased expression of PGC-1α may not be due to its related gene variants. PGC-1α could become a candidate blood-based biomarker for diagnosis and monitoring disease progression. [ABSTRACT FROM AUTHOR]