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Introduction Tobacco kills nearly 6 million people per year on account of direct tobacco use or indirect smoke exposure [World Health Organization (WHO) 2014]. Cigarette smoking, the primary method of [...], BACKGROUND: Smoking is a risk factor for many human diseases. DNA methylation has been related to smoking, but genome-wide methylation data for smoking in Chinese populations is limited. OBJECTIVES: We aimed to investigate epigenome-wide methylation in relation to smoking in a Chinese population. METHODS: We measured the methylation levels at > 485,000 CpG sites (CpGs) in DNA from leukocytes using a methylation array and conducted a genome-wide meta-analysis of DNA methylation and smoking in a total of 596 Chinese participants. We further evaluated the associations of smoking-related CpGs with internal polycyclic aromatic hydrocarbon (PAH) biomarkers and their correlations with the expression of corresponding genes. RESULTS: We identified 318 CpGs whose methylation levels were associated with smoking at a genome-wide significance level (false discovery rate < 0.05), among which 161 CpGs annotated to 123 genes were not associated with smoking in recent studies of Europeans and African Americans. Of these smoking-related CpGs, methylation levels at 80 CpGs showed significant correlations with the expression of corresponding genes (including RUNX3, IL6R, PTAFR, ANKRD11, CEP135 and CDH23), and methylation at 15 CpGs was significantly associated with urinary 2-hydroxynaphthalene, the most representative internal monohydroxy-PAH biomarker for smoking. CONCLUSION: We identified DNA methylation markers associated with smoking in a Chinese population, including some markers that were also correlated with gene expression. Exposure to naphthalene, a byproduct of tobacco smoke, may contribute to smoking-related methylation. http://dx.doi.org/10.1289/ehp.1509834

Background: The success of Duchenne muscular dystrophy gene therapy requires promising tools for gene delivery and mini-gene cassettes that can express therapeutic levels of a functional protein. Aims: To explore the expression feasibility of truncated dystrophin cDNAs mediated by a lentiviral vector derived from feline immunodeficiency virus. Materials and Methods: Three truncated dystrophin cDNAs were constructed by PCR cloning, then these cDNAs were inserted into lentiviral vectors. Recombinant lentiviruses were generated by transient transfection of lentiviral vector constructs into 293Ad5+ cells. Cultured myoblasts were then infected with recombinant lentiviruses. Expression of truncated dystrophin cDNAs was detected by Western blot analysis. Results: Mediated by lentiviral vectors, three cDNAs constructed by PCR cloning expressed relative truncated dystrophins in cultured myoblasts. Conclusions: Truncated dystrophin cDNAs can express themselves successfully mediated by feline immunodeficiency virus vectors. It offers the possibility of an approach utilizing truncated dystrophin cDNAs and lentiviral vectors toward gene therapy of Duchenne muscular dystrophy. [ABSTRACT FROM AUTHOR]

Coronary heart disease (CHD) is a leading cause of morbidity and mortality around the world and has both genetic and environmental precipitants. Genetic factors are significant in determining the level of risk factors in individuals. Variants in ZFHX3 gene are associated with atrial fibrillation in individuals of European ancestry. The aim of this study was to analyze the polymorphisms in the compositionally biased region of the ZFHX3 gene in patients with coronary heart disease in a Chinese population, and to explore their associations with coronary heart disease. We recruited 278 CHD patients and 358 age and sex matched healthy controls in a Chinese Han population, polymorphisms in the compositionally biased region of the ZFHX3 gene were determined by polymerase chain reaction followed by DNA sequencing. The genotype frequencies were calculated, and statistical analysis was performed using the non-parametric mood median test. A complex insertion/deletion polymorphism was identified in the compositionally biased region of the ZFHX3 gene in a Chinese population. Six common genotypes (GGC)4GGTGGCAGT(GGC)4GGT(GGC)8, (GGC)4GGTGGCAGT(GGC)5GGT(GGC)8, (GGC)4GGTGGCAGT(GGC)5GGT(GGC)7, (GGC)2GGTGGCAGT(GGC)5GGT(GGC)10, (GGC)4GGTGGCAGT(GGC)5GGT(GGC)5, and (GGC)4GGT(GGC)8 were found in both CHD patients and healthy controls, there was no significant difference in the six genotype frequencies between CHD patients and healthy controls. Rare genotypes (GGC)4GGTGGCAGT(GGC)2GGT(GGC)2GGT(GGC)6, (GGC)4GGTGGCAGT (GGC)8, (GGC)4GGTGGCAGT(GGC)(3)GGT(GGC)8, and (GGC)6GGT(GGC)8 were only identified in healthy controls. Rare genotypes (GGC)4GGTGGCAGT(GGC)4GGT(GGC)5, (GGC)4GGTGGCAGT(GGC)4GGT(GGC)4, and (GGC)4GGTGGCGGT(GGC)6 were only found in CHD patients. The compositionally biased region of the ZFHX3 gene contains a poly-Gly sequence. A complex insertion/deletion polymorphism exists in this region in a Chinese population, clinical significance of some rare genotypes should be explored for CHD in the future.

Objective: To analyze the chromosome aberration in a full-term male neonate with low birth weight, and to explore the possible causes for growth retardation in intrauterine development for the neonate., Methods: Genomic DNA was extracted from peripheral leukocytes of the neonate. Detection of genomic DNA copy number gain and loss was performed using microarray comparative genomic hybridization. Chromosome karyotype was obtained from cultured lymphocytes for the neonate and his parents in order to identify the origin of chromosome aberration., Results: Gain of 10q25.2-->qter (22 Mb) was observed in the full-term neonate with low birth weight. In addition, one chromosomal region, 15q26.2-->qter (5 Mb) was lost. The karyotype of the neonate was 46, XY, -15, +der(15), t(10;15)(q25;q26)pat., Conclusion: The full-term neonate with low birth weight had a partial trisomy of 10q25.2-->qter with a partial monosomy of 15q26.2-->qter, both of them may contribute to the growth retardation in intrauterine development for the neonate case.

Objective: To identify an inbred Chinese pedigree with autosomal recessive muscular dystrophy and analyze the molecular defects., Methods: Linkage analysis was conducted using short tandem repeat(STR) markers from the regions associated with limb-girdle muscular dystrophy type 2A(LGMD2A) through 2H. Multi-Western blot was performed with anti-calpain-3, anti-dysferlin, anti-gamma-sarcoglycan, anti-alpha-sarcoglycan, and anti-dystrophin monoclonal antibodies. Mutation was determined by reverse transcriptase-polymerase chain reaction and sequencing., Results: Two-point linkage analysis showed significant Lod scores with markers from chromosome 2p13, the highest two-point Lod scores were obtained with D2S337 (Z(max)=1.86 at theta=0). Multi-Western blot confirmed dysferlin deficiency of muscle specimen from the proband. Mutation analysis revealed a novel 6429delG mutation on exon 53 of the DYSF gene for the proband., Conclusion: The authors identified an inbred Chinese pedigree with Miyoshi myopathy caused by a 6429delG on the DYSF gene. This mutation is predicted to result in premature termination of translation.