[Effects of restraint position on changes of diaphragmatic mechanical characteristic in rats].

OBJECTIVE: To observe effects of restraint position on the changes of diaphragmatic mechanical characteristic in rats, and try to explore the role of nitric oxide (NO). METHODS: Rat model of restraint position was established. Rats were divided into control group, restraint position 12h and 24h groups. The markers of respiratory functions in vivo and the biomechanical markers of diaphragmatic characteristic ex vivo were evaluated. Serum NO levels were measured with spectrophotometry. The expressions of nNOS and iNOS mRNA in diaphragm were detected using RT-PCR. RESULTS: Compared with control group, respiratory rate, tidal volume and minute ventilation were significantly decreased in the restraint position 12h and 24h groups. Pt of diaphragm significantly decreased and force-generating capacity reduced at low frequency stimulation in 12h group. Force-generating capacity over the full range reduced at low and high frequency stimulation in 24h group. Pt of diaphragm in control and restraint position groups increased after L-NNA pre-incubation. Force-frequency relationship after L-NNA pre-incubation reduced in 24h group. NO level in serum increased significantly in the restraint position groups. Diaphragmatic nNOS mRNA expression was upregulated significantly in the restraint position groups. CONCLUSION: Restraint position induces the decreasement of diaphragmatic contractility and the decreasement is mediated by NO from diaphragm or circulation blood.

An insertion/deletion polymorphism in the 3' untranslated region of type I collagen a2 (COL1A2) is associated with susceptibility for hepatocellular carcinoma in a Chinese population.

Hepatocellular carcinoma (HCC) is one of the most common and severe diseases in the world. Besides the influence of environmental factors, such as viral infection, an increasing number of novel genetic components identified by genome-wide association studies have been associated with predisposition to HCC. Thus, studies focusing on functional variants in these findings are indispensable. In the present study, based on in-silico analysis, we carried out a case-control study in a Chinese population (207 cases and 245 controls) to investigate the association between HCC susceptibility with a 7 base pair (bp) insertion/deletion polymorphism (rs3917) in the 3'UTR of COL1A2. Our results showed that the ins/del + del/del genotype had an odds ratio of 1.76 (95% C.I.=1.03-3.01; P=0.028) for developing HCC compared to the ins/ins genotype. Carriers for the "del" allele of rs3917 were associated with a 1.73-fold increased risk for HCC (95% C.I.=1.06-2.84; P(trend)=0.02). Computational modeling suggests that this polymorphism is located in the hsa-let-7 g potential target sequence in the COL1A2 3' untranslated region. Our data suggest that most likely, common genetic changes in COL1A2 may influence HCC risk, at least in part by let-7 g-mediated regulation, which is possibly involved in the pathogenesis of HCC. The replication of our studies in other populations will further strengthen our understanding of this association.

Association of HLA-G 3' UTR 14-bp insertion/deletion polymorphism with hepatocellular carcinoma susceptibility in a Chinese population.

The 14-bp insertion/deletion (indel) polymorphism located in the 3' UTR of the human leukocyte antigen-G (HLA-G) gene plays a role in several autoimmune and chronic inflammatory diseases. HLA-G expression is associated with hepatocellular carcinoma (HCC) prognosis, especially in early stage, with high expression independently associated with shortened overall survival and increased tumor recurrence. In the present study, we carried out a case-control study in a Chinese population (318 cases and 599 controls) to estimate the susceptibility to HCC associated with the 14-bp indel polymorphism. Logistic regression analysis showed that the heterozygote and the homozygote 14-bp ins/ins confer a lower risk of HCC (adjusted OR = 0.75, 95% CI: 0.57-1.01, p = 0.061; OR = 0.54, 95% CI: 0.30-0.98, p = 0.031, respectively). Hepatitis B virus (HBV) stratification analysis showed that the associations were stronger in the HBV-positive population. Immunohistochemical analysis further showed that HLA-G expression in HCC tissues with 14-bp del/del genotype was more prominent than for heterozygous and 14-bp ins/ins genotype (p < 0.01). Taken together, our results suggested that the HLA-G 14-bp indel polymorphism may be a marker for genetic susceptibility to HCC in Chinese populations. Further studies from different populations with larger sample size are warranted to validate our findings.

Association of the pentanucleotide repeat polymorphism in NOS2 promoter region with susceptibility to migraine in a Chinese population.

Genes involved in the production of nitric oxide (NO) have been suggested as genetic factors for migraine. It has been studied whether polymorphisms in the genes encoding for different types of NO synthase (NOS) could be involved in the liability to migraine; however, most studies yield negative results. The pentanucleotide repeat microsatellite in the promoter region of inducible NOS (NOS2) shows highly significant differences in allelic frequencies among ethnically diverse populations. Thus, variation in the number of pentanucleotide repeats may have some significance in the predisposition to migraine among different human populations. The aim of this study was to investigate the possible association between pentanucleotide repeat polymorphism and the risk for migraine in Chinese population. We studied the genotypic and allelic frequencies of the pentanucleotide repeat polymorphism in the promoter region of NOS2 in 504 patients with migraine and 512 healthy controls, using polymerase chain reaction amplification and polyacrylamide gel electrophoresis analyses. Comparison of global allele counts between patients and controls showed that the difference was significant (p = 0.0014). The carriage of 9-repeat and 10-repeat alleles was significantly more common in controls, whereas 11-repeat allele was more common in patients after Bonferroni correction for multiple comparisons. A specific analysis of the different cutoffs for number of repeats showed that allelic and genotypic frequencies for the 9-repeat and 10-repeat cutoff were significantly different between cases and controls (p = 0.007 and p = 0.005 for allelic frequencies, respectively; p = 0.0086 and p = 0.0033 for genotypic frequencies, respectively). Our results implied an association between NOS2 pentanucleotide repeat polymorphism and migraine susceptibility in a Chinese population. Considering the significant allelic frequency differences in ethnically diverse populations, further replication studies, especially in ethnically different groups, were necessary to fully establish the role of NOS2 polymorphism in migraine susceptibility.

Lack of association between ADRA2B-4825 gene insertion/deletion polymorphism and migraine in Chinese Han population.

OBJECTIVE: The present study aimed to estimate the association between susceptibility to migraine and the 12-nucleotide insertion/deletion (indel) polymorphism in promoter region of alpha(2B)-adrenergic receptor gene (ADRA2B). METHODS: A case-control study was carried out in Chinese Han population, including 368 cases of migraine and 517 controls. Genomic DNA was extracted from blood samples, and DNA fragments containing the site of polymorphism were amplified by PCR. Data were adjusted for sex, age, migraine history and family history, and analyzed using a logistic regression model. RESULTS: There was no association between indel polymorphism and migraine, at either the allele or the genotype level. CONCLUSION: These findings do not support a functional significance of ADRA2B indel polymorphism at position -4825 relative to the start codon in the far upstream region of the promoter in the present migraine subjects.

The vascular endothelial growth factor-2549 insertion/deletion polymorphism is not associated with susceptibility to hepatocellular carcinoma in Chinese.

Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis, which is crucial for development and metastasis of tumors including hepatocellular carcinoma (HCC), and elevated VEGF levels in serum and tissues have been known to be related with poor prognosis in patients with HCC. Polymorphisms in VEGF may alter VEGF protein concentrations, influence the process of angiogenesis, and may relate to interindividual variation in tumorigenesis. In this study, we carried out a case-control study in a Chinese population (206 cases and 302 controls) to estimate the susceptibility to HCC associated with an 18-bp insertion/deletion polymorphism (rs35569394) in the promoter region of VEGF. After adjusting the data by gender, age, smoking status, drinking status, and hepatitis B virus (HBV) infection using logistic regression model, we found that rs35569394 was not associated with HCC, at both the allele and genotype levels. Thus, rs35569394 should not be viewed as a major contributor to the development of HCC in Chinese.

An insertion/deletion polymorphism in the 3' untranslated region of beta-transducin repeat-containing protein (betaTrCP) is associated with susceptibility for hepatocellular carcinoma in Chinese.

Hepatocellular carcinoma (HCC) is an epithelial cancer which originates from hepatocytes or their progenitors. As a positive regulator of NFkappaB signaling pathway, beta-transducin repeat-containing protein (betaTrCP) is overexpressed and oncogenic in epithelial cancers, suggesting a potential role of betaTrCP in HCC susceptibility. We carried out a case-control study in a Chinese population (256 cases and 367 controls) to estimate the susceptibility to HCC associated with a 9bp insertion/deletion polymorphism (rs16405) in 3' untranslated region of betaTrCP. Using unconditional logistic regression, we found that 9N del/del and 9N ins/del genotypes were significantly associated with decreased HCC risk: OR=0.44 (0.24-0.83) (p=0.004) and OR=0.56 (0.31-1.00) (p=0.034), respectively. Furthermore, in vivo experiments showed that mRNA levels of betaTrCP from HCC tumor tissues were correlated with rs16405 genotypes. HCC tumor tissues with homozygous for 9N ins/ins has the highest level of betaTrCP, which are 3.99 and 7.04-fold higher than heterozygous 9N ins/del and homozygous 9N del/del, respectively. Based on bioinformatics prediction, we found that the risk allele for rs16405 disrupted a binding site for human microRNA-920 which would negatively regulate betaTrCP. We propose a microRNA-920 mediated betaTrCP regulation model depending on rs16405 genotype, which warrants further replication association studies and follow-up functional experiments.