Association of the TNF-α+489 G/A polymorphism with chronic obstructive pulmonary disease risk in Asians: meta-analysis.

The association between the TNF-α +489 G/A polymorphism and chronic obstructive pulmonary disease (COPD) remains controversial because of small group size and varied design among different studies. In the present study, a meta-analysis was conducted to assess the association between the +489 G/A polymorphism and COPD risk. A comprehensive search was conducted to identify articles that have reported an association between the TNF-α +489 G/A polymorphism and COPD risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under both dominant (AA+GA vs GG genotypes) and allele (A vs G) models. Heterogeneity was assessed, as well as publication bias. Nine articles with ten eligible studies were included in this analysis. Significant association between the +489 G/A polymorphism and COPD was identified in Asians under the allele model (OR = 1.582, 95%CI = 1.035-2.419). However, no significant difference was found in the Caucasian groups. Strong evidence for between-study heterogeneity was identified under both models, and no publication bias was detected. Our results indicated a potential role of the A allele of the TNF-α +489 G/A polymorphism in increasing COPD risk in Asians, but not in Caucasians. Additional studies will be necessary to verify this conclusion.

Proton pump inhibitor use and risk of spontaneous bacterial peritonitis in cirrhotic patients: a systematic review and meta-analysis.

We used a meta-analysis approach to investigate the association between proton pump inhibitor (PPI) use and risk of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. We searched Ovid Medline, Embase, and the Cochrane Library to identify eligible studies. We included studies that compared cirrhotic patients who did or did not use PPIs. The primary outcome was SBP, and the secondary outcome was overall bacterial infection. Results were pooled using random-effect models. This process led to identification of 12 journal articles and 5 conference abstracts. The pooled data showed that PPI use in patients with cirrhosis and ascites was significantly associated with an increased risk of SBP [odds ratio (OR) = 2.17; 95% confidence interval (CI) = 1.46-3.23; P < 0.05; I2 = 85.6%] and overall risk of bacterial infection (OR = 1.98; 95%CI = 1.36-2.87; P < 0.05; I2 = 0). Subgroup analysis revealed that journal articles and studies reporting adjusted effect estimates demonstrated that PPI users had a significantly increased risk of SBP (OR = 2.13; 95%CI = 1.61-2.82; P < 0.05; I2 = 29.4%; and OR = 1.98; 95%CI = 1.42-2.77; P < 0.05; I2 = 67%, respectively). In conclusion, PPI use increased the risk of SBP and overall bacterial infection in patients with cirrhosis and ascites. PPIs should be administered after careful assessment of the indications in cirrhotic patients. Future well-designed prospective studies are warranted to clarify the dose relationships and to compare infection risks associated with different classes of PPIs.

Cloning and expression analysis of a heat shock protein 90 ß isoform gene from the gills of Wuchang bream (Megalobrama amblycephala Yih) subjected to nitrite stress.

Heat shock protein 90 (HSP90), a highly conserved and multi-functional molecular chaperone, plays an essential role in cellular metabolism and stress response. In this study, HSP90 cDNA named MaHSP90 was cloned from Wuchang bream (Megalobrama amblycephala) gills by using rapid amplification of cDNA ends. The full-length MaHSP90 cDNA is 2674 bp and consists of a 3',5'-untranslated region and a 2250-bp open reading frame encoding a 750-amino acid long protein. Identity analysis revealed that the amino acid sequence of MaHSP90 is highly conserved. Homology analysis and structure comparison further indicated that MaHSP90 should be the ß isoform member of the HSP90 family. MaHSP90 mRNA was ubiquitously expressed in the liver, heart, muscle, gill, intestine, kidney, and brain. The MaHSP90 mRNA levels under nitrite stress were analyzed using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR); the mRNA levels significantly increased at 3, 6, and 12 h after nitrite exposure in the gills and then stabilized between 24 and 48 h. Furthermore, a similar relationship between mRNA expression (qRT-PCR) and HSP90 protein levels (densitometric band analysis) was found. Transcriptional analysis of caspase-8 and caspase-9 expression in the gills of juvenile M. amblycephala after a 48-h exposure to nitrite suggested that MaHSP90 expression is related positively with nitrite-induced apoptosis. Fish exposed to nitrite also showed gill damage. Our results suggest that MaHSP90 mRNA is constitutively expressed in various tissues and inducible in the gills under nitrite stress, suggesting its important role in nitrite stress response.

Characterization of the male-specific lethal 3 gene in the oriental river prawn, Macrobrachium nipponense.

In this study, male-specific lethal 3 homolog (Mnmsl3) was cloned and characterized from the freshwater prawn Macrobrachium nipponense (Crustacea: Decapoda: Palaemonidae) by rapid amplification of cDNA ends. The deduced amino acid sequences of Mnmsl3 showed high-sequence homology to the insect Msl3 and contained a conserved chromatin organization modifier domain and an MORF4-related gene domain. Real-time quantitative reverse transcription-polymerase chain reaction showed that the Mnmsl3 gene was expressed in all the investigated tissues, with the highest level of expression in the testis. The expression level of Mnmsl3 between males and females was different in the gonad (testis or ovary), abdominal ganglion, and heart. The results revealed that the Mnmsl3 gene might play roles in regulating chromatin and in dosage compensation of M. nipponense. Real-time quantitative reverse transcription-polymerase chain reaction also revealed that Mnmsl3 mRNA expression was significantly increased in both 5 and 20 days post-larvae after metamorphosis, suggesting that Mnmsl3 plays complex and important roles in the early embryonic development and sex differentiation of M. nipponense.

Different timing and spatial separation of parental chromosomes in intergeneric somatic hybrids between Brassica napus and Orychophragmus violaceus.

Experimental and newly formed hybrids and polyploids generated by wide crosses usually show varying degrees of cytological instability. The spatial separation of parental genomes and uniparental chromosome elimination in hybrid cells has been reported in many hybrids from plants and animals. Herein, the behavior of parental genomes in intergeneric somatic hybrids between Brassica napus and Orychophragmus violaceus was analyzed using genomic in situ hybridization (GISH). In mitotic and meiotic cells, the chromosomes from O. violaceus were distinguished from B. napus by their larger size and staining patterns. In interphase nuclei of the hybrid, O. violaceus-labeled chromatin appeared as large heterochromatic blocks that were nonrandomly distributed at prophase, typically distributed toward one side of the nucleus. In pollen mother cells at prophase I of meiosis, O. violaceus chromosomes appeared as one or two deeply stained chromatin blocks that resolved into bivalents at a late stage, after bivalents from B. napus were visible. Thereafter, bivalents of O. violaceus congressed to the equatorial plate and segregated at anaphase I after those from B. napus. The different behavior of O. violaceus chromosomes in the hybrids indicates that they have differential condensation states at interphase and progress later through the cell cycle and meiosis than B. napus chromosomes. This difference in behavior may restrict or prevent the formation of bivalents of mixed genome origin. Differential gene expression of parental alleles including rDNA loci may contribute to their distinct cytological behavior and to the phenotype of hybrids.

Role of the RUNX2 p.R225Q mutation in cleidocranial dysplasia: a rare presentation and an analysis of the RUNX2 protein structure.

Cleidocranial dysplasia (CCD; MIM 119600) is an autosomal dominant hereditary disorder of skeletal features whose characteristic clinical symptoms are caused by mutations in the RUNX2 gene. Varying degrees of clavicular hypoplasia and dental abnormalities are the most prominent features of this disorder. In this study, we presented a Chinese family that included 4 individuals with a p.R225Q mutation in the RUNX2 gene and characteristic CCD phenotypes. Through structural analysis of the p.R225Q mutation in the RUNX2 protein, we determined that the location of this mutation has the potential to affect DNA binding by RUNX2. The proband in this CCD-affected family showed a specific clinical phenotype of CCD that included a median pseudo-cleft palate, which is a presentation of this mutation that has not been reported previously. On the basis of the structural analysis, this study further demonstrated that the p.R225Q mutation abolished DNA binding by RUNX2 and its results also suggested that other genetic and/or environmental factors could affect the CCD phenotypes.

Association of -238G/A and -863C/A polymorphisms in the TNF-α gene with chronic obstructive pulmonary disease based on a meta-analysis.

Chronic obstructive pulmonary disease (COPD) is a chronic systemic inflammatory disease; increasing evidence indicates that the TNF-α polymorphism is associated with progression of this disease. Few studies have focused upon association between TNF-α -238G/A or -863C/A polymorphism and COPD risk. Reported associations have been controversial because of small sample size and varied study design among the different studies. We performed a meta-analysis to assess the correlation of these two polymorphisms in the TNF-α gene with COPD risk. A comprehensive search was conducted to identify all published articles on the association between TNF-α -238G/A or -863C/A polymorphism and COPD risk from different databases. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated, and the heterogeneity and publication bias were assessed. Eight articles with 10 eligible studies met our inclusion criteria; six studies were of the -238G/A polymorphism and the others involved the -863C/A polymorphism. In the case of the -863C/A polymorphism, significant association was detected only in Asians in the A allele carriers (GA+AA versus GG genotype) and allele (A versus G allele) model (OR = 0.505, 95%CI = 0.321-0.795 and OR = 0.560, 95%CI = 0.368-0.851, respectively). However, no significant association was detected for the -238G/A polymorphism. No evidence of between-study heterogeneity and publication bias was detected. We suggest a potentially protective role of the A allele in the TNF-α -863C/ A polymorphism against developing COPD in Asians. This hypothesis needs further studies for confirmation.

Association of the G403A polymorphism in the RANTES gene with coronary artery disease: a meta-analysis.

The G403A polymorphism in the RANTES (regulated on activation normal T cell expressed and secreted) gene has a key role in the expression of RANTES, which has been detected in a range of cells in atherosclerotic plaque. However, the association of this polymorphism with the risk of coronary artery disease (CAD) remains controversial. A meta-analysis was performed to assess the association of the G403A polymorphism in the RANTES gene with the risk of CAD. A comprehensive search was conducted to identify all studies published on the association of the RANTES gene G403A polymorphism with CAD risk. The fixed or random-effect pooled measure was adopted based on a heterogeneity test among studies, which was evaluated using I(2). Potential sources of between-study heterogeneity were explored using meta-regression analysis. Publication bias was estimated with Begg's rank correlation method. Eight articles were included in this meta-analysis, with 4601 CAD cases and 2522 controls. No significant association of RANTES gene G403A polymorphism with CAD was identified in any of the codominant, dominant, recessive, homozygote, or heterozygote inheritance models. No evidence of publication bias was detected. The meta-analysis suggested that the A allele of the G403A polymorphism in the RANTES gene has no effect on the risk of CAD. This relationship needs to be confirmed by further studies.