Association of genetic polymorphisms in HSD17B1, HSD17B2 and SHBG genes with hepatocellular carcinoma risk.

Genetic polymorphisms of enzymes involved in estrogen synthesizing/transporting can influence the risk of hormone-dependent diseases. The incidence rate and relative risk for hepatocellular carcinoma (HCC) are higher in men than in women. This study was conducted to explore the relationship of single nucleotide polymorphisms (SNPs) in 17 ß-Hydroxysteroid dehydrogenases (HSD17B1 and HSD17B2) and sex hormone-binding globulin (SHBG) genes with the risk of HCC within Chinese Han population. Polymorphisms of HSD17B1 rs676387, HSD17B2 rs8191246 and SHBG rs6259 were genotyped in 253 HCC patients and 438 healthy control subjects using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Significantly increased HCC risk was found to be associated with T allele of rs676387 and G allele of rs8191246. Increased HCC risks were found in different genetic model (TT genotype in a recessive model, T allele carriers in a dominant model, TT genotype and TG genotype in a codominant model for HSD17B1 rs676387, G allele carriers in a dominant model and AG genotype in a codominant model for HSD17B2 rs8191246, respectively). No association between SHBG rs6259 and HCC risk was observed. The present study provided evidence that HSD17B1 rs676387 and HSD17B2 rs8191246 were association with HCC development. Further studies in diverse ethnic population with larger sample size were recommended to confirm the findings.

Influence of angiotensin I-converting enzyme gene polymorphism on hepatocellular carcinoma risk in China.

Growing evidence suggests that the angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) genes are associated with risk in a wide range of cancers. The objective of this study was to examine whether two DNA polymorphisms at the ACE insertion/deletion (I/D) and the variable number of tandem repeats in NOS intron 4 (4a/4b) were linked to the risk of developing hepatocellular carcinoma (HCC) in a Chinese population. The polymorphisms at ACE I/D and eNOS 4a/4b were genotyped in 293 HCC patients and 384 healthy control subjects using polymerase chain reaction. The frequencies of the D allele (p=0.003, OR=0.72, 95% CI=0.58-0.90) in the ACE gene of HCC patients were significantly different from the healthy controls, and a significantly decreased HCC risk was associated with the DD genotype in both the recessive (p<0.001, OR=0.19, 95% CI=0.11-0.34) and codominant models (p<0.001, OR=0.26, 95% CI=0.14-0.48). This study provided evidence that the ACE I/D polymorphism is associated with HCC, indicating that the ACE I/D polymorphism contributes to HCC progression in the Chinese population.

Expression of basigin in the early phase of acute myocardial ischemia in rats.

Basigin may be involved in cardiovascular disease. In our previous study, suppression subtractive hybridization results indicated that basigin may be associated with the early phase of acute myocardial ischemia (AMI) within 1 h. However, little is known regarding the expression of basigin in the early phase of AMI. The aim of the present study was to evaluate the temporal and spatial expression patterns of basigin mRNA and protein levels in AMI in rats. We constructed an AMI model in rats that received left anterior descending coronary artery ligation for 0, 15, 30, 60, 120 or 240 min. Real­time quantitative PCR and in situ hybridization (ISH) were conducted to reveal the basigin mRNA levels in the early ischemic myocardium (EIM) and non­ischemic myocardium (NIM). The expression levels of basigin protein were detected using western blot analysis and immunohistochemistry. The expression levels of basigin mRNA and protein significantly changed in the EIM as early as 30 min from ischemia, and the changes continued to be present throughout the ischemic period (P<0.05). The expression levels of basigin mRNA were significantly reduced, whilst those of the protein underwent a significant ~2-fold increase in the EIM. However, there were no significant differences in the basigin mRNA or protein expression levels from 0­240 min in the NIM (P>0.05). We failed to detect a signal for basigin mRNA in the myocardium by ISH. Our findings indicated that basigin may be involved in acute myocardial ischemia following continual ischemia for >30 min.

[Expression of SSB following early myocardial ischemia in rats].

OBJECTIVE: To investigate the expression of Sjögren's syndrome antigen B (SSB) gene and SSB protein in the early ischemic myocardium in rats. METHODS: Adult healthy Sprague-Dawley rats were randomly divided into groups of operation [myocardial ischemia (MI) and non-ischemia (NI)], non-operation (NO) and sham-operation (SO) (n = 6 for MI and NI; n = 4 for NO and SO). According to time of ischemia, it was then divided into groups of 0 min, 15 min, 30 min, 60 min, 120 min, and 240 min. The expression of SSB gene in the myocardium was examined by real-time PCR, and the expression of SSB protein was examined by Western blot and immunofluorescence staining. RESULTS: The expressions of SSB gene was down-regulated at early stage of ischemia. There was significant difference between 0 min and 120 min at the level of expression of SSB gene in MI group, so did that between 120 min group and NO group (P < 0.05). The expression of SSB protein at 60 min after ischemia was significantly decreased compared with that in the group of 0 min (P < 0.05). The expression of SSB protein in NI groups was significantly higher than that in MI groups at the time of 60 min and 120 min after myocardial ischemia (P < 0.05). Additionally, the expression of SSB protein was mainly located in the myocardial nucleus, myocardial plasma, and plasma membrane of partial myocardiocytes according to the result of immunofluorescence staining. CONCLUSION: SSB may participate in pathophysiologic regulation process in myocardial cells at the early stage of myocardial ischemia in rats.

Interactions of interleukin-12A and interleukin-12B polymorphisms on the risk of intracranial aneurysm.

Several lines of evidence indicate that inflammatory processes play pivotal role in the development of intracranial aneurysm (IA). Recently, polymorphisms in the interleukin-12 (IL-12) gene were shown to be associated with immune-mediated inflammatory disease. The aim of this study was to investigate the interactions of IL-12A and IL-12B polymorphisms on the risk of IA in a Chinese population. A total of 422 individuals (including 164 patients with IA and 258 controls) were involved in the study. The polymorphisms (i.e., rs2243115 and rs568408 in IL-12A and rs3212227 in IL-12B) were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay and DNA sequencing. We found an association of the AC/CC genotypes and C allele of IL-12B rs3212227 with an increased risk of IA, compared with the AA genotype and A allele (AC/CC vs. AA: OR = 2.09, 95 % CI: 1.29-3.38; C vs. A: OR = 1.45, 95 % CI: 1.10-1.91). Moreover, a significant gene interaction of IL-12A and IL-12B was evident on the risk of IA, and subjects carrying variant genotypes of IL-12B rs3212227 had an increased risk of IA. In the stratified analysis by gender, the IL-12B rs3212227 AC/CC genotypes had an increased risk of IA compared with the AA genotype in male patients (AC/CC vs. AA: OR = 4.63, 95 % CI: 1.92-11.16). These findings suggest that the IL-12A and IL-12B independently and jointly be involved in the susceptibility to IA.

Association between pri-miR-218 polymorphism and risk of hepatocellular carcinoma in a Han Chinese population.

MicroRNAs are noncoding RNA molecules of 18-25 nucleotides that regulate gene expression at the post-transcriptional level. The aim of this study was to investigate whether pri-miR-218 rs11134527 A/G polymorphism influences the risk of hepatocellular carcinoma (HCC) or not. pri-miR-218 rs11134527 A/G was genotyped in 302 HCC patients and 513 control subjects using the polymerase chain reaction-restriction fragment length polymorphism assay. The AG genotype of pri-miR-218 rs11134527 A/G was associated with family history (p=0.018, odds ratio [OR]=2.96, 95% confidence interval [CI]: 1.16-7.56) and elevated serum α-fetoprotein (serum alpha-fetoprotein [AFP]) levels (≥20 ng/mL; p=0.009, OR=1.92, 95% CI: 1.17-3.14) in HCC patients. These findings suggested that the AG genotype of pri-miR-218 rs11134527 might relate to genetic predisposition and be involved in regulating the expression of AFP in Chinese HCC patients.

The association between MLH1 -93 G>A polymorphism of DNA mismatch repair and cancer susceptibility: a meta-analysis.

DNA mismatch repair, known as a fundamentally biological pathway, plays key roles in maintaining genomic stability, eliminating mismatch bases and preventing both mutagenesis in the short term and cancerogenesis in the long term. Polymorphisms of MLH1 in individuals may have an effect on the DNA repair capacity and therefore on cancer risk. Recently, emerging studies have been done to evaluate the association between MLH1 -93 G/A polymorphism and cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. In this meta-analysis, we assessed reported studies of association between the MLH1 -93 G/A polymorphism and cancer risk including 13 691 cancer cases and 14 068 controls from 17 published studies. A borderline significant association between the MLH1 -93 G/A polymorphism and cancer risk was observed in overall analysis [heterozygote: odds ratio (OR) = 1.15; 95% confidence interval (CI) 1.05-1.26; homozygote: OR = 1.21; 95% CI, 1.04-1.40; dominant model: OR = 1.13; 95% CI 1.01-1.26; recessive model: OR = 1.21; 95% CI 1.07-1.35, respectively]. In subgroup analysis by ethnicity, significantly increased risks were found in Asian population and mixed population but not in Caucasian population. After stratified analysis according to the quality of literature, increased cancer risks were observed in the studies of lower quality but not in the studies of higher quality. Similarly, elevated cancer risks were observed in hospital-based studies but not in population-based studies. These findings showed no persuasive evidence that MLH1 -93 G/A polymorphism was associated with an increased risk of cancer. On the conservative standpoint, well-designed population-based studies with larger sample size in different ethnic groups should be performed to further confirm these results.

The association between two polymorphisms in pre-miRNAs and breast cancer risk: a meta-analysis.

Emerging evidence has shown that miRNAs participate in human carcinogenesis as tumor suppressors or oncogenes. Single nucleotide polymorphism (SNP) which located in the pre-miRNA may affect the processing and then influence the expression of mature miRNA. Previous studies yielded conflicting results as to the association of two common polymorphisms in pre-miRNAs (i.e. hsa-miR-146 rs2910164 and hsa-miR-196a2 rs11614913) with breast cancer. To derive a more precise effect on the association between these polymorphisms and breast cancer risk, we conducted a meta-analysis. Through retrieving PubMed for the period up to May 2010, a total of four studies were identified with 3,007 cases and 3,718 controls for has-miR-146a rs2910164 polymorphism and with 3,287 cases and 4,298 controls for hsa-miR-196a2 rs11614913 polymorphism. We found that individuals carrying CC genotype of has-miR-196a2 rs11614913 polymorphism was associated with an increased breast cancer risk in homozygote comparison (OR = 1.30; 95% CI, 1.01-1.68), and dominant model (OR = 1.11; 95% CI, 1.01-1.23). However, no significant association between has-miR-146a rs2910164 polymorphism and breast cancer risk was observed in all comparison models tested. These findings suggest that has-miR-196a2 rs11614913 polymorphism may play crucial roles in breast cancer development.

RAD51 135G/C polymorphism and breast cancer risk: a meta-analysis from 21 studies.

Growing evidence suggests that RAD51 plays a pivotal role in the repair of DNA double-strand breaks and the maintenance of genomic stability. A single nucleotide polymorphism, 135G/C, has been identified in the 5' untranslated region of the RAD51 gene and has been shown to influence gene transcription activity. Previous studies yielded conflicting results as to the association of 135G/C polymorphism with breast cancer. We aimed to assess the effect of 135G/C of RAD51 on breast cancer susceptibility with the use of a meta-analysis. We performed a meta-analysis of 21 published case-control studies up to April 2010. We found that the CC genotype was associated with a significantly increased risk of breast cancer when compared with the GG, CG, and CG/GG genotypes. Subgroup analyses showed that individuals carrying the CC genotype were associated with an elevated tumor risk in European populations and in sporadic breast cancer. After stratified analyses according to manuscript quality, the CC genotype was associated with a significantly increased risk of breast cancer compared with the CG genotype in studies of both higher and lower quality. However, significantly elevated risk was found in studies of higher quality, but not in studies of lower quality when homozygote and a recessive comparison model were tested. This meta-analysis indicates that RAD51 135G/C polymorphism may be identified as a susceptibility locus for breast cancer.

CTLA4 and CD86 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) may be related to chronic inflammation and immune-mediated conditions, and its pathogenesis involves T-cell activation and proliferation. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and costimulatory molecules (CD80/CD86) genes are important mediators of T-cell activation in the immune response. The aim of this study was to investigate whether +2379G/C (rs17281995) and +1057G/A (rs1129055) in CD86 and -318C/T (rs5742909) and +49A/G (rs231775) in CTLA-4 genes single nucleotide polymorphisms (SNPs) are associated with COPD in a Chinese population. The four polymorphisms were identified in 396 COPD patients and 400 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequency of the T allele of the -318C/T in CTLA-4 and the A allele of the +1057G/A in CD86 polymorphisms showed significant association with COPD when compared with controls (T allele: p < 0.0001; A allele: p = 0.009). Comparison of genotype frequencies showed that -318CT, +1057GA, and +1057AA genotype was overrepresented in the COPD group, respectively (-318CT: 50.8% vs 28.5%, p < 0.0001; +1057GA: 58.6% vs 54.2%, p = 0.002; +1057AA: 30.1% vs 25.8%, p = 0.002). However, we failed to find any association between the four SNPs and COPD when cases were classified by smoking status or clinical stages (p > 0.05). The results indicate that the polymorphisms of CTLA-4 (-318C/T) and CD86 (+1057G/A) may be important genetic factor associated with risk or protection for COPD in Chinese population.

[Expression of SSB gene in rats with early isehemic myocardium and its implications].

OBJECTIVE: To examine the expression of Sjögren's syndrome antigen B (SSB) gene in rats with early ischemic myocardium. METHODS: Adult healthy Sprague-Dawley rats were randomly divided into four groups (ischemia (MI), non-ischemia (NI), sham-operated (SO) and normal control (NO) groups). The expression of SSB and beta-actin gene in the myocardium was examined by real time PCR at 0 min, 5 min, 15 min, 30 min, 60 min, 120 min after ligation of the left anterior descending coronary artery (LAD). RESULTS: The expression of SSB gene was down-regulated after ischemia. Significantly lower expression of the gene in the rats with myocardial ischemia was found at 120 min after ligation compared with those before ligation and the control group at 120 min after ligation (P < 0.05 ). However, no significant differences were found between other groups (P > 0.05). CONCLUSION: SSB gene may be involved in the pathophysiologic regulating process in myocardial cells at the early stage of myocardial ischemia in rats.

[The expression of Basigin mRNA in early ischemic myocardium and non-ischemic myocardium].

OBJECTIVE: To investigate the expression of Basigin mRNA in early ischemic myocardium (EIM) and non-ischemic myocardium (NIM) in rat. METHODS: Real-time polymerase chain reaction (PCR) technique was applied for detecting Basigin mRNA and beta-actin expression in EIM and NIM at 0 min, 15 min, 30 min, and 60 min. RESULTS: No significant differences of the Basigin mRNA expression in EIM and NIM between 0 min and sham operation (SO) or non-operation group (P > 0.05) were observed. Basigin mRNA expression in EIM significantly decreased in 15 min, 30 min, and 60 min group compared with that of 0 min group, respectively (P < 0.001). However, we failed to find any significant difference in NIM and NO from 0 min to 60 min. Basigin mRNA expression in EIM decreased significantly compared with that of in NIM (P < 0.05) after myocardial ischemia for 30 min. CONCLUSION: Basigin was involved in myocardium pathophysiology process after myocardial ischemia for 30 min, indicating that Basigin may be identified as a predictor of early myocardial ischemia in forensic medicine.

[Study on the distribution and location of neuroglobin in human tissues and cells].

OBJECTIVE: To explore the distribution and location of neuroglobin (NGB) and its function in human tissues and cells. METHODS: The distribution and localization of NGB in human tissues and cells were examined by immunohistochemical method. RESULTS: NGB-positive cells were mainly distributed in neurons of central nervous system and peripheral nervous system, and some in endocrine tissues and genital system. NGB-immunoreactive product located in the cytoplasm of these cells. CONCLUSION: The expression of NGB in human nervous tissues, some endocrine tissues and genital system suggested that NGB might play an important role in the utilizations of oxygen and physiological functions.