Association and expression study of MMP3, TGFβ1 and COL10A1 as candidate genes for leg weakness-related traits in pigs

The present study was aimed to determine the association between metalloproteinase 3 (MMP3), transforming growth factor beta 1 (TGF??1) and collagen type X alpha I (COL10A1) gene polymorphisms with traits related to leg weakness in pigs. Three hundred Duroc?×?Pietrain cross breds (DuPi) and 299 pigs of a commercial population (CP) were used for the experiment. DuPi animals were examined for 10 different traits describing leg and feet structure, osteochondrosis (OC) scores and bone density status. Data of OC score at condylus medialis humeri, condylus medialis femoris and distal epiphysis ulna regions of CP were used for association analysis. Significant association (P?<?0.05) was found for MMP3 SNP (g.158 C>T) with OC at head of femur and bone mineral density in the DuPi population. Association (P?<?0.05) was found between SNP of TGF??1 (g.180 G>A) with rear leg score and the principle component denoting both OC and feet and leg scores in the DuPi population. No association was found between COL10A1 (g.72 C>T) and leg weakness related traits. The associations of SNPs with OC traits could not be confirmed in the commercial population. Expression analysis of the three candidate genes was performed to compare between healthy and OC. TGF??1 was found to be highly expressed (P?<?0.05) in the OC compared to healthy cartilages, but no significant different expressions were observed for MMP3 and COL10A1 genes. The present finding suggested that TGF??1 and MMP3 genes variants have an effect on some of the leg weakness related traits.     

Hydrolytic Enzyme Production is Associated with Candida Albicans Biofilm Formation from Patients with Type 1 Diabetes

Oral candidosis is common in patients with diabetes mellitus, as yeasts, particularly Candida albicans, have the propensity to colonise, form biofilms and release hydrolytic enzymes which cause inflammation. This study aimed to investigate these characteristics in isolates from three groups of patients with type 1 diabetes: individuals with better controlled diabetes (BCD; ≥6 <8%), individuals with poorly controlled diabetes (PCD; ≥8%) and non-diabetics (ND; HbA_1c <5.9%). The biomass (Bm), phospholipase (P_z), haemolysin (H_z) and proteinase (Pr_z) were assessed using a microtitre biofilm assay and agar-based hydrolytic enzyme assays. Biofilm formation was significantly increased in the PCD group compared to ND and BCD groups (P < 0.05). No significant differences in P_z levels were observed between groups, whereas both H_z and Pr_z were significantly greater in the diabetes groups than in the healthy control group (P < 0.05). Statistically significant correlations were found to exist between the HbA_1c levels of the patients and the Bm (R = 0.384; P = 0.033), haemolysin activity (R = ?0.455; P = 0.010) and proteinase activity (R =  ?0.531; P = 0.002). There was no apparent correlation between the Bm and P_z activity (R = ?0.305; P = 0.053) or H_z activity (R = ?0.100; P = 0.296). However, a negative correlation was found between Bm and Pr_z values (R = ?0.343; P = 0.030). These data suggest that biofilm formation is likely to play a role in the pathogenicity of oral candidosis, and in patients with diabetes, this may be due to the ability of C. albicans to adapt to the altered physiological environment. The production of hydrolytic enzymes is independently associated with this growth modality.     

Genetic polymorphisms in the CYP1A1 and CYP1B1 genes and susceptibility to bladder cancer: a meta-analysis

The current meta-analysis of case–control studies was conducted to evaluated the relationships of genetic polymorphisms in the CYP1A1 and CYP1B1 genes with the susceptibility to bladder cancer, aiming at determine whether these polymorphisms may contribute to the pathogenesis of bladder cancer. Related articles were determined via searching the following electronic databases without any language restrictions: PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases for relevant articles published before November 1st, 2013. STATA 12.0 software was also selected to deal with statistical data. The relationships were evaluated using the pooled odds ratios (ORs) and their 95 % confidence intervals (CI). Eleven case–control studies with a total of 2,609 bladder cancer patients and 2,634 healthy subjects met the inclusion criteria. The results of our meta-analysis demonstrated that CYP1A1 genetic polymorphisms were associated with increased risks of bladder cancer (allele model: RR = 1.18, 95 % CI 1.07–1.30, P = 0.001; dominant model: RR = 1.15, 95 % CI 1.05–1.27, P = 0.003; respectively), especially among 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms. A subgroup analysis by ethnicity was conducted to investigate its effect on susceptibility to bladder cancer. The subgroup analysis results revealed positive significant correlations between CYP1A1 genetic polymorphisms and bladder cancer risk among Asians (allele model: RR = 1.26, 95 % CI 1.10–1.44, P = 0.001; dominant model: RR = 1.22, 95 % CI 1.08–1.38, P = 0.001), but not among Caucasians (all P < 0.05). Nevertheless, we observed no significant correlations between CYP1B1 genetic polymorphisms and bladder cancer risk (all P > 0.05). Our meta-analysis indicates that CYP1A1 genetic polymorphisms may be involved in the pathogenesis of bladder cancer, especially among 11599G>C, 2455A>G, 3810T>C, and 113T>C polymorphisms. However, CYP1B1 genetic polymorphisms may not be important determinants of bladder cancer susceptibility.     

Association between colony-stimulating factor 1 receptor gene polymorphisms and asthma risk

Colony-stimulating factor 1 receptor (CSF1R) is expressed in monocytes/macrophages and dendritic cells. These cells play important roles in the innate immune response, which is regarded as an important aspect of asthma development. Genetic alterations in the CSF1R gene may contribute to the development of asthma. We investigated whether CSF1R gene polymorphisms were associated with the risk of asthma. Through direct DNA sequencing of the CSF1R gene, we identified 28 single nucleotide polymorphisms (SNPs) and genotyped them in 303 normal controls and 498 asthmatic patients. Expression of CSF1R protein and mRNA were measured on CD14-positive monocytes and neutrophils in peripheral blood of asthmatic patients using flow cytometry and real-time PCR. Among the 28 polymorphisms, two intronic polymorphism (+20511C>T and +22693T>C) were associated with the risk of asthma by logistic regression analysis. The frequencies of the minor allele at CSF1R +20511C>T and +22693T>C were higher in asthmatic subjects than in normal controls (4.6 vs. 7.7%, p = 0.001 in co-dominant and dominant models; 16.4 vs. 25.8%, p = 0.0006 in a recessive model). CSF1R mRNA levels in neutrophils of the asthmatic patients having the +22693CC allele were higher than in those having the +22693TT allele (p = 0.026). Asthmatic patients with the +22693CC allele also showed significantly higher CSF1R expression on CD14-positive monocytes and neutrophils than did those with the +22693TT allele (p = 0.045 and p = 0.044). The +20511C>T SNP had no association with CSF1R mRNA or protein expression. In conclusion, the minor allele at CSF1R +22693T>C may have a susceptibility effect in the development of asthma, via increased CSF1R protein and mRNA expression in inflammatory cells.     

Novel SNPs in the bovine ADIPOQ and PPARGC1A genes are associated with carcass traits in Hanwoo (Korean cattle)

Adiponectin (ADIPOQ) modulates several biological processes including energy homeostasis, glucose and lipid metabolism. The bovine ADIPOQ gene was located near the QTL affecting marbling, ribeye muscle area and fat thickness on BTA1. The gene encoding peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) was located within the QTL region of the traits on BTA6. Moreover, its protein product has various biological functions such as cellular energy homeostasis, including adaptive thermogenesis, adipogenesis and gluconeogenesis. Therefore, the ADIPOQ and PPARGC1A genes are a positional and functional candidate gene for carcass traits in beef cattle. The objectives of this study were to identify polymorphisms in the bovine ADIPOQ and PPARGC1A genes, to evaluate their associations with carcass traits in Hanwoo (Korean cattle) population. We identified nine SNPs in the ADIPOQ gene. Two SNPs (DQ156119: g.1436T > C and DQ156119: g.1454A > G) in the promoter region were recognized as new SNPs identified in Hanwoo. Association analysis indicated that the g.1454A > G SNP genotype was significantly associated with effects on LMA (P = 0.004) and BF (P = 0.021). The ADIPOQ haplotype was also found to have significant effect on the LMA. In the PPARGC1A gene, we identified 11 SNPs in the two unexplored regions (intron 3 and 5). Among them, seven SNPs were located in intron 3 and four SNPs were located in intron 5. Of these 11 putative novel SNPs, two SNPs (AY839822: g.292C > T and AY839823: g.1064C > T) with minor allele frequency (MAF) > 0.20 were examined for associations with carcass traits. The association analysis revealed that both SNPs in PPARGC1A gene were significantly associated with LMA (P < 0.05). These findings suggest that the SNPs of bovine ADIPOQ and PPARGC1A genes may be a useful molecular marker for selection of carcass traits in Hanwoo.     

Genetic Diversity of the Melanocortin 4 Receptor (MC4R) Gene and its Association with Slaughter Traits in the Landes Goose

Melanocortin 4 receptor (MC4R) plays a crucial part in regulating feeding behavior in humans and rodents. We detected two single nucleotide polymorphisms (SNPs; c.108G → A and c.627C → T) in the goose MC4R gene and genotyped 94 Landes geese for association analysis with several carcass traits. Significant associations (P < 0.05) were obtained for c.108G → A with carcass weight, breast muscle percentage, and leg muscle percentage, and for c.627C → T with body weight, carcass weight, semi-eviscerated weight, and eviscerated weight. We re-constructed haplotypes based on the two SNPs and analyzed diplotypes in association with carcass traits, obtaining significant associations with several of the traits. These results suggest that polymorphisms in the MC4R gene could have effects on carcass traits in Landes geese. More study is required to confirm these results.     

Identification of novel SNPs in the Sarda breed goats POU1F1 gene and their association with milk productive performance

The aim of the study was to detect polymorphism in the POU1F1 gene in Sarda breed goat, as well as to establish if SNPs could be associated with milk productive traits. The research was conducted on 129 Sarda breed goats from 4 to 5 years old, multiparous, lactating and in their third to fifth lactation. We report nine exonic and seven non-coding regions SNPs within the Sarda goat POU1F1 gene, namely, Ex 1 61 G>C; Ex 1 108 G>A; Ex 3 C>T; Ex 3 92 C>T; Ex 4 110 A>G; Ex 5 34 G>A resulting in Arg213Lys change; IVS4 641 G>A, IVS4 643 A>C, IVS4 659 G>A, IVS4 677 A>C, IVS4 G699Del, IVS4 709 C>G, Ex 6 17 G>A resulting in Arg228Ser change, Ex 6 58 G>T, Ex 6 172 T>C, 3′UTR 110 T>C. A statistically significant association was found between genotype TT, in position 17 of the exon 6 (3.1 % of frequency), and increased milk yield (P < 0.01) while genotype GT (25.6 % of frequency) was associated with a higher fat content. Genotype TT in position 58 of the exon 6 (3.9 % of frequency) was found to be associated with a higher fat (P < 0.01) and protein content (P < 0.05). Twenty-eight haplotypes were detected, but no significant association between the haplotypes and the milk production traits have been found. Our data, as well as providing new SNPs extending the POU1F1 gene characterization, evidence a relationship between polymorphism and milk production traits in Sarda goat breed.     

Association of CYP1A1 and CYP2D6 gene polymorphisms with head and neck cancer in Tunisian patients

The purpose of this study was to investigate the relationship between head and neck cancer (HNC) and environmental agents and polymorphisms in CYP1A1, CYP2D6, NAT1 and NAT2 metabolic enzymes genes. To the best of our knowledge, this is the first report on polymorphisms in CYP1A1 6310C>T, CYP2D6 Arg365His, NAT1 52936A>T and NAT2 Arg268Lys (NAT2*12A) genes and susceptibility to HNC in Tunisian population. We study the prevalence of these polymorphisms in 169 patients with HNC and 261 control subjects using polymerase chain reaction based methods in a Tunisian population. We detected an association between HNC and CYP1A1 6310C>T (TT) and CYP2D6 Arg365His (His/His) variant carriers (OR 1.75, P = 0.008 and OR 1.66, P = 0.016, respectively). No association was found between the polymorphisms genotypes of NAT1 52936T>A and NAT2 Arg268Lys and risk of HNC. An association between HNC and CYP1A1 (TT) genotype was found among patients with smoking (P = 0.011) and drinking habit (P = 0.009). The combinations of NAT1 (AT or AA) and NAT2 (AA) at-risk genotypes increased HNC risk (OR 4.23, P = 0.005 and OR 3.60, P = 0.048, respectively). However, the combinations of CYP1A1 (AA) and CYP2D6 (CC) genotypes decreased risk of HNC (OR 0.20; P = 0.006). Genetic polymorphisms in CYP1A1 and CYP2D6 may significantly associate with HNC in the Tunisian population. The results of this study suggest a possible gene–environment interaction for certain carcinogen metabolizing enzymes, but larger studies that fully evaluate the interaction are needed.     

Effects of single and combined genotypes of MC4R and POU1F1 genes on two production traits in Langshan chicken

The objective of this study was to analyze the effects of single and combined genotypes of MC4R and POU1F1 genes in Chinese well-known indigenous chicken (Langshan chicken) population. Genetic variants within MC4R gene and POU1F1 gene were screened through PCR-SSCP and DNA sequencing methods. A C/T mutation at nt 944 in MC4R gene (NC_006089.2:g. 944C>T) and a G/A mutation at nt 3109 in POU1F1 gene (NC_006088.2:g. 3109 G>A) were identified. Associations between the mutations of the two genes with two production traits were analyzed. The results showed that, at MC4R locus, individuals with BB and AB genotypes had highly significantly higher body weight at 16 weeks (p < 0.01) than did those with the AA genotype. And, individuals within AA and AB genotypes had significantly higher egg numbers at 300 days (p < 0.05). At POU1F1 locus, individuals with CD genotype had higher body weight at 16 weeks and egg numbers at 300 days (p < 0.05). Furthermore, combined genotypes from these two loci were found to be associated with egg numbers at 300 days (p < 0.05). The individuals within combined genotype AB/CD had higher egg production. Therefore, variations identified within the MC4R and POU1F1genes are suitable for future use in identifying chickens with the genetic potential of higher body weight and reproductive traits, at least in the population of Langshan chickens.     

CRP Gene polymorphism contributes genetic susceptibility to dyslipidemia in Han Chinese population

C-reactive protein (CRP), an inflammatory marker that statistically predicts future cardiovascular risk, has been reported to be associated with plasma lipid level changes. Whether CRP genetic variants affect lipid metabolism is of importance to investigate. A community-based study population including 2,731 adult subjects aged 18–62 years was used to evaluate the association of CRP gene with dyslipidemia and five tagging SNPs (tagSNPs) were genotyped. Multiple logistic regression was applied to further evaluate relationships between the SNPs and lipid metabolism abnormality and general linear model was applied to compare plasma lipid levels between genotypes. Association analyses indicated that recessive model of SNPs rs876537 and rs4285692 had significant association with elevated HDL after adjustment for covariates. Odds ratio (OR) of rs876537 were 0.60 for HDL > 1.54 versus 1.04–1.54 mmol/L (P = 0.011), as well as, ORs were 0.617 for HDL > 1.83 versus ≤1.35 mmol/L (P = 0.002) and 0.724 for HDL = 1.59–1.83 versus ≤1.35 mmol/L (P = 0.028) respectively. OR of rs4285692 was 0.634 for HDL > 1.83 versus ≤1.35 mmol/L (P = 0.027). Further stratification analysis found significant associations of rs10737175 with elevated HDL (>1.54 vs. 1.04–1.54 mmol/L, OR 0.629 and P = 0.027) and elevated TG (≥1.70 vs. <1.70 mmol/L, ORs of additive and dominant models were 0.628, 0.545 and P values were 0.006, 0.003 respectively) in female. rs4285692 was significantly associated with elevated LDL (≥3.37 vs. <3.37 mmol/L), ORs equaled to 1.532, 2.281 for additive model and recessive model and P values were 0.028, 0.024 respectively in male. Furthermore, quantitative trait analysis indicated the variation T to C of rs876537 significantly affect decreased plasma HDL level (P = 0.014). Our findings suggest that CRP genetic polymorphisms independently had positive association with the risk of HDL, LDL and TG elevating and further replication in other large population and biological function research would be warranted.     

Linkage map construction using InDel and SSR markers and QTL analysis of heading traits in Brassica oleracea var. capitata L.

Cabbage heading traits are important quantitative traits that greatly affect both quality and yield of cabbage. However, the genetic control of these traits remains unclear. To detect quantitative trait loci (QTLs) associated with heading traits, a double haploid (DH) population with 196 lines was created from a cabbage hybrid 01–20 × 96–100. A genetic map with insertion–deletion and simple sequence repeat markers was constructed based on the DH population, with a total length of 934.06 cM and average interval length of 2.3 cM between adjacent markers. Field experiments in three seasons were carried out to evaluate the heading traits, including head mature period (Hm), head weight (Hw), core length (Cl), head vertical diameter (Hvd), and the ratio of Cl to Hvd (Cl/Hvd). Using the map and the trait data, 13 reliable QTLs in total were identified and 5 were found in more than one season based on the adjusted means of three seasons. Major QTLs were identified for Hm (R ² = 40.4, LOD = 14.84), Hw (R ² = 28.6, LOD = 9.83), Cl (R ² = 38.8, LOD = 15.73), Hvd (R ² = 19.2, LOD = 9.26), and Cl/Hvd (R ² = 38.8, LOD = 12.75). The most significant QTLs were Hm3.1, Cl3.1, and Cl/Hvd3.1, which were detected in three seasons with the maximum contribution rate of almost 40 %. Six active regions that harbored more than one QTL were identified on five chromosomes, and one of them contained major QTLs associated with five traits. The QTLs obtained in this study should be useful for marker-assisted selection in cabbage breeding and for understanding the genetic control of these traits.     

Association between the rs6950982 polymorphism near the SERPINE1 gene and blood pressure and lipid parameters in a high-cardiovascular-risk population: interaction with Mediterranean diet

The SERPINE1 (serpin peptidase inhibitor, clade E, member 1) gene, better known by its previous symbol PAI-1 (plasminogen activator inhibitor 1), has been associated with cardiovascular phenotypes with differing results. Our aim was to examine the association between the rs6950982 (G > A) near the SERPINE1 gene, blood pressure (BP) and plasma lipid concentrations as well as the modulation of the polymorphism effects by adherence to Mediterranean diet (AMD). We studied 945 high-cardiovascular-risk subjects. Biochemical, clinical, dietary and genetic data (rs6950982) were obtained. We also determined the common rs1799768 (4G/5G), for checking independent effects. AMD was measured by a validated questionnaire, and four groups were considered. rs6950982 (A > G) and rs1799768 (4G/5G) were only in moderate–low linkage disequilibrium (D′ = 0.719; r ² = 0.167). The most significant associations we obtained were with rs6950982 (A > G). In males, the G allele was nominally associated with higher diastolic BP (AA: 81.5 ± 10.9, AG: 82.1 ± 11.4, GG: 85.7 ± 10.5 mmHg; P _additive = 0.030) and systolic BP (AA + AG: 141.4 ± 6.9 mmHg vs. GG: 149.8 ± 8.0 mmHg; P _recessive = 0.036). In the whole population, the rs6950982 was also associated with plasma lipids. Subject with the G allele presented higher total cholesterol (P _additive = 0.016, P _recessive = 0.011), low-density lipoprotein cholesterol (P _additive = 0.032, P _recessive = 0.031) and triglycerides (P _additive = 0.040, P _recessive = 0.029). AMD modulated the effect of rs6950982 on triglyceride concentrations (P for interaction = 0.036). Greater AMD reduced the higher triglyceride concentrations in GG subjects. No significant interactions were found for the other parameters. The rs6950982 was associated with higher BP in men and higher triglycerides in the whole population, this association being modulated by AMD.     

Genetic variations of HSBP1 gene and its effect on thermal performance traits in Chinese Holstein cattle

Molecular chaperones have been understood to be preferentially transcribed to prevent perturbations in response to various stresses. In this study, three single nucleotide polymorphisms (SNPs), g.324G>C, g.589C>T and g.651C>G in Heat shock factor binding protein 1 (HSBP1) gene were found and genotyped in 930 Chinese Holstein cattle. The results indicated that only g.589C>T polymorphism locus met Hardy–Weinberg equilibrium (P > 0.05). Pair linkage disequilibrium analysis and haplotype construction of HSBP1 gene were performed using SHEsis software. Seven haplotypes were constructed and fourteen haplotype combinations were found. Association analysis showed that H2H2 haplotype combination was advantageous for thermo tolerance breeding in Chinese Holstein. The cows with H2H2 haplotype combination have lower decrease rate of milk yield than those with H2H3 haplotype combination (P < 0.05) and lower potassium content in erythrocytes (PCE) than those with H2H5 (P < 0.05), H4H4 (P < 0.05) and H4H5 (P < 0.01) haplotype combination. The association between SNP and thermo tolerance traits showed that PCE of cows with GG genotype was lower than those with CG genotype at g.651C>G locus (P < 0.01). Pair linkage disequilibrium analysis revealed that the three loci were at a strong disequilibrium state. So we presumed that the effect of H2H2 haplotype combination on thermo tolerance traits major due to the SNP of g.651C>G.     

Cashmere production,skin characteristics,and mutated genes in crimped cashmere fibre goats

A subpopulation of Yanshan cashmere goats with crimped fibre has emerged in a closed population in recent years, but little is known about differences in cashmere production performance, skin characteristics, and fibre-style-related genes between goats with different cashmere fibre styles. Therefore, the aim of this study was to investigate fibre characteristics, cashmere yield, hair follicle traits, and fibre-style-related genes in cashmere goats with the two cashmere fleece styles—non-crimped and crimped. Based on the cashmere fibre type, 80 six-month-old female Yanshan cashmere goats were used in this study: 40 goats with non-crimped fleece (NCF) and 40 with crimped fleece (CF). The growth performance and cashmere production of the goats were recorded. Skin samples were collected to determine hair follicle traits and gene sequencing. The results indicated that there were no differences in initial live weight, final live weight, average daily feed intake, and average daily gain between the two groups of goats (P > 0.05). The total yield of cashmere and the stretched length of fibre of the CF goats were higher (P < 0.01 and P < 0.05, respectively) and fibre diameter was lower (P < 0.05) than that of the NCF goats. There were no between-group differences in the density and activity of primary and secondary hair follicles, secondary-to-primary fibre ratio, depth of primary follicles, or epidermal thickness. However, the depth of secondary follicles and dermal thickness were higher (P < 0.05) in NCF goats than in CF goats. There were mutations in the KRT5, KAP8, KRT8, KRT74, KRT34, KRT1, KRT71, KRT6A, KAP6, KRT81, and KRT83 genes, four of which caused amino acid changes. The allele and genotype frequencies of base mutations in the KRT5, KAP8, KRT34, KRT1, KRT6A, KRT81, and KRT83 genes were different in the NCF and CF goats (P < 0.05). The distribution and content of the secondary structure elements and tertiary structures of proteins differed between the wide-type and mutated KRT1 and KRT6A proteins. KRT1, KRT6A, KRT71, and TGFα mRNA expression levels were significantly higher in CF goats than in NCF goats (P < 0.05). It is concluded that cashmere goats that have fleece with crimped fibres produce a greater yield of fleece with finer diameter fibres than those with conventional straight cashmere fibres. These differences in fibre properties may be associated with mutations in the genes coding for KRT1 and KRT6A.     

Common variants in the ATP2B1 gene are associated with hypertension and arterial stiffness in Chinese population

Genome-wide association studies have identified the ATP2B1 gene associated with blood pressure (BP), the evidence from large scale Chinese population was still rare. We performed the current replication study to test the association of the ATP2B1 gene and hypertension and BP in two unrelated Chinese cohorts including 2,831 unrelated individuals with hypertension and 1,987 controls in total. We also examined the influences of the ATP2B1 gene on the arterial stiffness through evaluation of carotid-femoral pulse wave velocities (cf-PWV) in 164 untreated hypertensives. The major findings of this study were that four loci––rs10858911, rs2681472, rs17249754 and rs1401982––associated with any or all of four traits: hypertension (P = 0.001–4.6E–05; odds ratio, 0.83–0.87), systolic BP (P = 0.003–0.004), diastolic BP (P = 0.002–0.003) and cf-PWV (P = 0.002–0.004). All the comparisons were adjusted for sex, age, age² and body mass index. We validated the association of the ATP2B1 gene and susceptibility to hypertension, BP traits and cf-PWV in Chinese population. In addition, further genetic and functional research was warranted to elucidate the concrete locus in the ATP2B1 gene that influenced the manifestation of BP and vascular function.     

A miR-570 binding site polymorphism in the B7-H1 gene is associated with the risk of gastric adenocarcinoma

Single nucleotide polymorphisms (SNPs) in putative microRNA (miRNA) target sites (miRSNPs) could affect the binding of miRNA with the target and contribute to the susceptibility of human cancers. However, the role of miRSNPs in gastric cancer susceptibility remains largely unknown. Since the over-expression of B7-H1 protein has been reported to be closely related to disease progression of gastric cancer, we investigated the possible role of miRSNPs at the 3′-untranslated region (3′-UTR) of B7-H1 in the risk of developing gastric cancer. In this association study on 205 gastric adenocarcinoma patients and 393 non-cancer controls, we found that the genotype distribution of a common C>G polymorphism (rs4143815) was significantly different between the cases and controls (P = 1.32 × 10^?8). Compared with CC homozygotes, GG homozygotes and G allele carriers showed 3.73-fold (P = 2.98 × 10^?8) and 1.85-fold (P = 0.002) increased risk of gastric adenocarcinoma, respectively. Stratified analyses indicated that variant genotypes had a strong association with the clinic-pathological features of gastric cancer including differentiation grade, depth of tumor infiltration, and tumor node metastasis (TNM) stage (P < 0.001). Luciferase reporter assay indicated that this SNP might be responsible for aberrant B7-H1 protein expression in gastric cancer by disrupting the interaction between miR-570 and B7-H1 mRNA. These results are consistent with our hypothesis and indicate that genetic polymorphisms influencing B7-H1 expression modify cancer susceptibility.     

Aberrant promoter methylation of RASSF1A gene may be correlated with colorectal carcinogenesis: a meta-analysis

We conducted a meta-analysis of cohort studies to evaluate the potential role of RASSF1A promoter methylation in colorectal carcinogenesis. A range of electronic databases were searched: PubMed (1966–2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980–2013), CINAHL (1982–2013), Web of Science (1945–2013) and the Chinese Biomedical Database (CBM) (1982–2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated. Eleven clinical cohort studies with a total of 1,505 colorectal cancer (CRC) patients that met all inclusion criteria were included in our meta-analysis. The results of our meta-analysis revealed that the frequency of RASSF1A promoter methylation was strongly correlated with clinical stage (OR = 1.69, 95 % CI 1.16–2.44, P = 0.006), histological grade (OR = 1.92, 95 % CI 1.22–3.04, P = 0.005) and distant metastasis (OR = 2.59, 95 % CI 1.46–4.60, P = 0.037) of CRC patients. However, we observed no positive correlations of RASSF1A promoter methylation with gender (OR = 1.04, 95 % CI 0.74–1.46, P = 0.842), age (OR = 1.70, 95 % CI 0.98–2.93, P = 0.057) and lymph node metastasis (OR = 1.65, 95 % CI 0.87–3.14, P = 0.127) of CRC patients. Further subgroup analysis by ethnicity demonstrated that RASSF1A promoter methylation was correlated with clinicopathological characteristics of CRC patients among Asians (clinical stage: OR = 2.55, 95 % CI 1.55–4.20, P < 0.001; histological grade: OR = 2.70, 95 % CI 1.44–5.06, P = 0.002; lymph node metastasis: OR = 4.09, 95 % CI 1.49–11.26, P = 0.006; distant metastasis: OR = 5.38, 95 % CI 1.73–16.70, P = 0.004), but not among Caucasians and Africans (all P > 0.05). Our meta-analysis has shown positive correlations between aberrant promoter methylation of RASSF1A gene and clinicopathological characteristics of CRC patients, especially among Asians.