Association of rare PPARGC1A variants with Parkinson's disease risk.

BACKGROUND: Recent researches on Parkinson's disease (PD) pathogenesis discovered the correlation between PD and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) dysfunction and reduction of PPARGC1A gene expression. Hence, we detected PPARGC1A rare variants to clarify their effect on PD risk in a large population of PD patients in mainland China. METHODS: We applied whole-exome sequencing (WES) to 1917 patients with early-onset or familial PD and 1652 controls (WES cohort), and whole-genome sequencing (WGS) to 1962 patients with sporadic late-onset PD and 1279 controls (WGS cohort). To identify PPARGC1A rare variants, we used burden analysis to assess the relationship between PPARGC1A rare variants and PD susceptibility. RESULTS: 30 rare missense variants in the cohort WES and 21 missense variants in the cohort WGS have been detected in the study and PPARGC1A missense variants are significantly associated with early-onset and familial PD susceptibility in our study (P = 0.012), which supports evidence that PPARGC1A rare variants are involved in the onset of early-onset and familial PD. CONCLUSIONS: The study suggested that PPARGC1A rare variants may contribute to the risk of early-onset and familial PD.

Evaluating the role of ARSA in Chinese patients with Parkinson's disease.

Recent studies have suggested ARSA, a gene responsible for metachromatic leukodystrophy, could be a genetic modifier of Parkinson's disease (PD) pathogenesis, acting as a molecular chaperone for α-synuclein. To elucidate the role of ARSA variants in PD, we did a comprehensive analysis of ARSA variants by performing next-generation sequencing on 477 PD families, 1440 sporadic early-onset PD patients and 1962 sporadic late-onset PD patients and 2636 controls from Chinese mainland, as well as the association between ARSA variants and cognitive function of PD patients. We identified 2 familial PD following autosomal dominant inherence carrying rare variants of ARSA, but they had limited clinical significance. We detected a total of 81 coding variants of ARSA in our subjects but none of the identified variants were associated with either susceptibility or cognitive performance of PD, while loss-of-function variants showed slightly increased burden in late-onset PD (0.25% vs. 0%, p = 0.08). Our results suggested ARSA may not play important roles in PD of Chinese population.

Multi-Omics Analyses Reveal the Regulatory Network and the Function of ZmUGTs in Maize Defense Response.

Maize is one of the major crops in the world; however, diseases caused by various pathogens seriously affect its yield and quality. The maize Rp1-D21 mutant (mt) caused by the intragenic recombination between two nucleotide-binding, leucine-rich repeat (NLR) proteins, exhibits autoactive hypersensitive response (HR). In this study, we integrated transcriptomic and metabolomic analyses to identify differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) in Rp1-D21 mt compared to the wild type (WT). Genes involved in pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI) were enriched among the DEGs. The salicylic acid (SA) pathway and the phenylpropanoid biosynthesis pathway were induced at both the transcriptional and metabolic levels. The DAMs identified included lipids, flavones, and phenolic acids, including 2,5-DHBA O-hexoside, the production of which is catalyzed by uridinediphosphate (UDP)-dependent glycosyltransferase (UGT). Four maize UGTs (ZmUGTs) homologous genes were among the DEGs. Functional analysis by transient co-expression in Nicotiana benthamiana showed that ZmUGT9250 and ZmUGT5174, but not ZmUGT9256 and ZmUGT8707, partially suppressed the HR triggered by Rp1-D21 or its N-terminal coiled-coil signaling domain (CCD21). None of the four ZmUGTs interacted physically with CCD21 in yeast two-hybrid or co-immunoprecipitation assays. We discuss the possibility that ZmUGTs might be involved in defense response by regulating SA homeostasis.

Correlation analysis between single nucleotide polymorphisms of pulmonary surfactant protein A gene and pulmonary tuberculosis in the Han population in China.

OBJECTIVE: To investigate the correlation of single nucleotide polymorphisms (SNPs) in SFTPA1 and SFTPA2 genes encoding pulmonary surfactant protein A (SP-A) with the susceptibility to pulmonary tuberculosis (PTB) in the Han population in China. METHODS: This study included 248 patients with active PTB (case group) and 124 normal individuals (control group). SNPs at loci aa19, aa50, aa62, aa133, and aa219 of SFTPA1, and at loci aa9, aa91, aa140, and aa223 of SFTPA2 were analyzed with PCR. Multivariate logistic regression analysis was used to identify the correlation of age, sex, and SNPs with PTB. RESULTS: The frequencies of the G allele at aa91 and T allele at aa140 in SFTPA2 were significantly higher in the case group than in the control group (p=0.0002 and p=0.045). The distribution of haplotype CGAAC in SFTPA1 was significantly lower in the case group than in the control group (p=0.025). In SFTPA2, the distributions of haplotypes 1A(6), 1A(10), 1A(9), and 1A(2) were higher (all p<0.05), but the distributions of haplotypes 1A(13), 1A(5), and 1A(12) were lower in the case group than in the control group (all p<0.05). When SFTPA1 and SFTPA2 were combined and analyzed, haplotype 6A(11)-1A(8) was only found in the case group (4.1%, p=0.001 compared with the control group), but the distribution of haplotype CGAAC-1A(0) or 6A(4)-1A(12) was significantly lower in the case group than in the control group (all p<0.05). CONCLUSIONS: SNP in SP-A is associated with PTB in the Han population in China. The G allele at aa91, T allele at aa140, and haplotype 6A11-1A8 are risk factors for PTB, but haplotype CGAAC-1A(0) and 6A(4)-1A(12) are protective factors for PTB.