Malignant Arrhythmia with Variants of Desmocollin-2 and Desmoplakin Genes.

Malignant arrhythmia is a fast cardiac arrhythmia that can lead to a hemodynamic abnormality within a short time, most of which is ventricular tachycardia or ventricular fibrillation (VF), which should be managed in time. Both organic and nonorganic cardiac diseases have the potential to cause malignant arrhythmia. We report a noteworthy case of malignant arrhythmia in a teenager during exercise. Transthoracic echocardiography, cardiac magnetic resonance (CMR), electrophysiological study, magnetic resonance imaging of the brain, electroencephalography, chest X-ray, and blood tests were all normal. Twelve-lead electrocardiography showed incomplete right bundle branch block (IRBBB). Two heterozygous missense variants of the desmocollin-2 gene (DSC2, c.G2446A/p.V816M) and desmoplakin gene (DSP, c.G3620A/p.R1207K) were detected in the peripheral blood of this teenager and his father by genetic testing, which encoded a desmosomal protein that was related to arrhythmogenic right ventricular cardiomyopathy (ARVC). In these two rare variants, DSC2 V816M has been reported but uncertain significance, whereas DSP R1207K is never reported. Therefore, the two site variants in DSC2 and DSP genes are likely to become a new research focus for diagnosis and treatment of ARVC in the future. Meanwhile, this report emphasizes that, in addition to a standard set of laboratory tests and examinations, genetic testing may be useful for analyzing the causes of malignant arrhythmia.

Rs12976445 Polymorphism Is Associated with Post-Ablation Recurrence of Atrial Fibrillation by Modulating the Expression of MicroRNA-125a and Interleukin-6R.

BACKGROUND This study aimed to identify the relationship between miR-125a polymorphism rs12976445 and the post-ablation recurrence of atrial fibrillation (AF), as well as to explore the underlying mechanism of miR-125a in AF recurrence. MATERIAL AND METHODS Microarray analysis was performed to search for miRNAs potentially involved in the regulation of AF recurrence, while real-time PCR (polymerase chain reaction) and Western blot analyses were carried out to study the expression of miR-125a (microRNA-125a), IL-6R (interleukin-6 receptor), and IL-16 (interleukin-16) in different experimental groups, so as to understand the regulatory relationships among miR-125a, IL-6R, and IL-16. Subsequently, a logistic regression analysis was utilized to investigate the survival status of recurrent AF in subjects harboring different genotypes of rs12976445. RESULTS The subjects in the GG and GC/CC groups of miR-125a polymorphism rs12976445 showed no obvious difference regarding all demographic characteristics that were collected in this study. In addition, 19 miRNAs were identified as potentially involved in the regulation of AF recurrence. Among these miRNAs, 6 were upregulated and 13 were downregulated in the group with early recurrence. According to real-time PCR results, the expression of miR-125a was dramatically upregulated in LRAF (late recurrence of atrial fibrillation) as well as in subjects harboring the GG genotype. On the contrary, the level of IL-6R mRNA was dramatically downregulated in LRAF and subjects harboring the GG genotype. Furthermore, IL-6R was confirmed as a candidate target of miR-125a by a luciferase reporter assay. CONCLUSIONS MicroRNA-125a polymorphism rs12976445 plays a role in AF recurrence via the regulation of IL-6R.

Association of polymorphisms in tektin-t gene with idiopathic asthenozoospermia in Sichuan, China.

PURPOSE: The purpose of this research was to study the association between the single nucleotide polymorphisms (SNPs) of the tektin-t gene and idiopathic asthenozoospermia. METHODS: We conducted sequence analyses of the tektin-t gene in 104 idiopathic asthenozoospermia and 102 fertile men with normospermic parameters in Sichuan, China. RESULTS: In this study, we found that allele 136 T (odds ratio [OR] 1.745, 95 % confidence interval [CI] 1.146-2.655, P = 0.009) was significantly increased in idiopathic asthenozoospermic patients compared with fertile men. This mutation substitutes a highly conserved arginine at position 46 to cysteine. Moreover, PolyPhen-2 analysis predicted that this variant was "probably damaging". In addition, a novel heterozygous mutation, R207H (c.620G >A), was detected in five asthenozoospermic patients, while there was no detection of this genotype among the fertile candidates, indicating that the mutation was located within a conserved domain predicted by PolyPhen-2 analysis as "probably damaging" to the protein. CONCLUSIONS: These results suggested that tektin-t variants (Arg/Cys + Cys/Cys) were probably one of the high risk genetic factors for idiopathic asthenozoospermia among males in Sichuan, China, while the R207H polymorphism may be associated with idiopathic asthenozoospermia risk.

[Effect of Winter Cover Cropping on Soil Greenhouse Gas Emissions in a Dryland Spring Maize Field on the Loess Plateau of China].

A field experiment was carried out to study the effects of winter cover cropping on soil greenhouse gas emissions in dryland maize. Four cover crop treatments, namely oat, lentil, a mixture of oat and lentil, and no cover crops (CK), were included during the winter fallow period. Greenhouse gas emission fluxes from soil were measured using the static chamber-gas chromatograph technique. The results showed that:both soil CO2 and N2O were emitted, but the soil acted as a sink for CH4. Compared with the that in CK, oat and lentil had no effect on the cumulative amount of soil CO2 emissions during the winter fallow period and increased the cumulative amount of soil CO2 emissions by 7.77% and 25.7% (P<0.05) in the spring maize growing period, respectively; the mixture increased the cumulative amount of soil CO2 emissions by 19.1% and 14.5% (P<0.05) during the winter fallow and spring maize growing periods. In the winter fallow and spring maize periods, compared with that in CK, oat declined the cumulative amount of soil N2O emissions by 11.6% and 14.7% (P<0.05), and lentil increased the cumulative amount of soil N2O emissions by 31.9% and 14.9% (P<0.05), respectively. Compared to that in the CK, the mixture declined the cumulative amount of soil N2O emissions by 19.2% (P<0.05) in the winter fallow period but had no effect in the spring maize period. Compared with the CK, oat, lentil, and their mixture resulted in a declined cumulative amount of soil CH4 uptake by 37.9%, 23.6%, and 29.6% (P<0.05) in the winter fallow period and by 19.4%, 33.5%, and 31.5% (P<0.05) in the spring maize growing period, respectively. Compared with the CK, oat had no effect on global warming potential (GWP), maize yield, and greenhouse gas intensity (GHGI). Lentil and the mixture increased GWP, and lentil showed a greater increase in GWP than that of the mixture. Compared with the CK, lentil and the mixture increased maize yield by 20.3% and 15.4% (P<0.05), respectively, and had no effect on GHGI. The findings from this study show that the lentil and oat mixture can significantly increase maize yield and decrease GHGI.

Association of polymorphisms in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) with idiopathic azoospermia or oligospermia in Sichuan, China.

The reported effects of the glutathione S-transferase (GSTs) genes (GSTM1, GSTT1, and GSTP1) on male factor infertility have been inconsistent and even contradictory. Here, we conducted a case-control study to investigate the association between functionally important polymorphisms in GST genes and idiopathic male infertility. The study group consisted of 361 men with idiopathic azoospermia, 118 men with idiopathic oligospermia, and 234 age-matched healthy fertile male controls. Genomic DNA was extracted from the peripheral blood, and analyzed by polymerase chain reaction and restriction fragment length polymorphism analysis. There was a significant association between the GSTP1 variant genotype (Ile/Val + Val/Val) with idiopathic infertility risk (odds ratio [OR]: 1.53; 95% confidence interval [CI]: 1.11-2.11; P = 0.009). Similarly, a higher risk of infertility was noted in individuals carrying a genotype combination of GSTT1-null and GSTP1 (Ile/Val + Val/Val) (OR: 2.17; 95% CI: 1.43-3.31; P = 0.0002). These results suggest an increased risk of the GSTP1 variant genotype (Ile/Val + Val/Val) for developing male factor infertility. Our findings also underrate the significance of the effect of GSTM1 and/or GSTT1 (especially the former) in modulating the risk of male infertility in males from Sichuan, Southwest China.

Transcriptional regulation of the apolipoprotein F (ApoF) gene by ETS and C/EBPα in hepatoma cells.

Apolipoprotein F (ApoF) inhibits cholesteryl ester transfer protein (CETP) activity and plays an important role in lipid metabolism. In the present study, the full-length human ApoF promoter was cloned, and the molecular mechanism of the regulation of ApoF was investigated. The ApoF promoter displayed higher activities in hepatoma cell lines, and the -198 nt to +79 nt promoter region contained the maximum promoter activity. In the promoter region of -198 nt to -2 nt there were four putative binding sites for transcription factors ETS-1/ETS-2 (named EBS-1 to EBS-4) and one for C/EBP. Mutation of EBS-2, EBS4 and the C/EBP binding site abolished the promoter activity, and ETS-1/ETS-2 and C/EBPα could interact with corresponding binding sites. In addition, overexpression of ETS-1/2 or C/EBPα enhanced, while dominant-negative mutants of ETS-1/2 and knockdown of C/EBPα decreased, ApoF promoter activities. ETS-1 and C/EBPα associated physically, and acted synergistically to activate ApoF transcription. These results demonstrated combined activation of the ApoF promoter by liver-enriched and ubiquitous transcription factors. Direct interactions between C/EBPα and ETS-1 were important for high liver-specific expression of ApoF.