Identification of transient receptor potential channel genes from the swimming crab, Portunus Trituberculatus, and their expression profiles under acute temperature stress.

BACKGROUND: Temperature is an important environment factor that is critical to the survival and growth of crustaceans. However, the mechanisms by which crustaceans detect changes in temperature are still unclear. The transient receptor potential (TRP) channels are non-selective cation channels well known for properties in temperature sensation. However, comprehensive understandings on TRP channels as well as their temperature sensing functions are still lacking in crustaceans. RESULTS: In this study, a total of 26 TRP genes were identified in the swimming crab, Portunus trituberculatus, which can be classified into TRPA, TRPC, TRPP, TRPM, TRPML, TRPN and TRPV. Tissue expression analysis revealed a wide distribution of these TRP genes in P. trituberculatus, and antennules, neural tissues, and ovaries were the most commonly expressed tissues. To investigate the responsiveness of TRP genes to the temperature change, 18 TRPs were selected to detect their expression after high and low temperature stress. The results showed that 12 TRPs showed induced gene expression in both high and low temperature groups, while 3 were down-regulated in the low temperature group, and 3 showed no change in expression in either group. CONCLUSIONS: This study characterized the TRP family genes in P. trituberculatus, and explored their involvement in response to temperature stress. Our results will enhance overall understanding of crustacean TRP channels and their possible functions.

Similarity of Chinese and Pakistani oral microbiome.

Oral microbiota is vital for human health and can be affected by various factors (i.e. diets, ethnicity). However, few studies have compared oral microbiota of individuals from different nationalities in the same environment. Here, we explored the assembly and interaction of oral microbial communities of Chinese and Pakistanis in one university. Firmicutes and Proteobacteria were the predominant microorganisms in the oral cavity of Chinese and Pakistanis. Streptococcus and Neisseria were the dominant genera of China, while Streptococcus and Haemophilus were the dominant genera of Pakistanis. In addition, the oral community membership and structure were not influenced by season, Chinese/Pakistani student and gender, reflecting the stability of the human oral microbiome. The beta diversity of oral microbiomes between Chinese and Pakistanis significantly differed in winter, but not in spring. The alpha diversity of Chinese students and Pakistani students was similar. Moreover, oral microbial community of both Chinese and Pakistani students was mainly driven by stochastic processes. The microbial network of Chinese was more complexity and stability than that of Pakistanis. Our study uncovers the characteristics of human oral microbiota, which is of great significance for oral and human health.

UHPLC-MS/MS Assay for Quantification of Legubicin, a Novel Doxorubicin-Based Legumain-Activated Prodrug, and Its Application to Pharmacokinetic and Tissue Distribution Studies.

Legubicin, a novel prodrug based on doxorubicin, has both albumin-binding and legumain-activating properties. The aim of this study was to develop and validate a UHPLC-MS/MS method for investigating the in vivo pharmacokinetics and tissue distribution profiles of legubicin in rats and tumor-bearing mice following intravenous administration, and to compare this prodrug with the positive control drug doxorubicin. The study employed a UHLC-MS/MS method to determine the levels of albumin-bound of legubicin and two metabolites (free Leu-DOX and DOX) in plasma, tumor, and tissue samples. This method was validated for good selectivity, high sensitivity, excellent extraction recovery, and short run time. The results showed that legubicin was present in the circulation in vivo mainly in a protein-bound form with larger AUC values and lower clearance and distribution, and essentially released small amounts of doxorubicin. Compared to administration of equimolar doses of doxorubicin, legubicin showed increased exposure of the active drug in the tumor and decreased the level of the active drug in the heart and kidney. This study provides valuable information on the pharmacokinetics and tissue distribution of legubicin, implicating its potential as a novel and effective drug candidate for anti-cancer therapies.

Cadaverine and putrescine exposure influence carbon and nitrogen cycling genes in water and sediment of the Yellow River.

The response patterns of microbial functional genes involved in biogeochemical cycles to cadaver decay is a central topic of recent environmental sciences. However, the response mechanisms and pathways of the functional genes associated with the carbon (C) and nitrogen (N) cycling to cadaveric substances such as cadaverine and putrescine remain unclear. This study explored the variation of functional genes associated with C fixation, C degradation and N cycling and their influencing factors under cadaverine, putrescine and mixed treatments. Our results showed only putrescine significantly increased the alpha diversity of C fixation genes, while reducing the alpha diversity of N cycling genes in sediment. For the C cycling, the mixed treatment significantly decreased the total abundance of reductive acetyl-CoA pathway genes (i.e., acsB and acsE) and lig gene linked to lignin degradation in water, while only significantly increasing the hydroxypropionate-hydroxybutylate cycle (i.e., accA) gene abundance in sediment. For the N cycling, mixed treatment significantly decreased the abundance of the nitrification (i.e., amoB), denitrification (i.e., nirS3) genes in water and the assimilation pathway gene (i.e., gdhA) in sediment. Environmental factors (i.e., total carbon and total nitrogen) were all negatively associated with the genes of C and N cycling. Therefore, cadaverine and putrescine exposure may inhibit the pathway in C fixation and N cycling, while promoting C degradation. These findings can offer some new insight for the management of amine pollution caused by animal cadavers.

Multi-omics methods reveal that putrescine and cadaverine cause different degrees of enrichment of high-risk resistomes and opportunistic pathogens in the water and sediment of the Yellow River.

Contamination of antibiotic resistomes due to animal carcass decay has become a serious environmental concern. However, the relationship between main metabolite compounds of corpse decomposition (i.e., putrescine and cadaverine) and antibiotic resistomes remains unclear. To tackle this issue, the response of antibiotic resistance genes (ARGs) and microbiome in aquatic environment to excess putrescine, cadaverine and a mixture of both based on laboratory simulation experiment was investigated by high-throughput quantitative PCR and amplicon sequencing methods. Our results showed putrescine and cadaverine led to the increasing of TC (total carbon) and TN (total nitrogen) both in water and sediment. Under the exposure of putrescine and cadaverine, the total abundance of mobile genetic elements (MGEs) and most ARGs in water was higher than in sediment. In particular, putrescine and cadaverine caused significantly different decreases in alpha diversity of microbial community in water and sediment compared with the control group. Microbial community structures both in water and sediment were also significantly affected by cadaverine and putrescine. Furthermore, putrescine and cadaverine led to different degrees of increases of high-risk ARGs (like mecA) and opportunistic pathogens (like Delftia) in sediment, promoting the prevalence of antibiotic resistant bacteria. In conclusion, our findings revealed the influences of main metabolites of carcass decay on microbiome and resistomes, providing references for risk assessment and pollution management.

Mammalian carcass decay increases carbon storage and temporal turnover of carbon-fixing microbes in alpine meadow soil.

Corpse decomposition is of great significance to the carbon cycle of natural ecosystem. Carbon fixation is a carbon conversion process that converts carbon dioxide into organic carbon, which greatly contributes to carbon emission reduction. However, the effects of wild animal carcass decay on carbon-fixing microbes in grassland soil environment are still unknown. In this research, thirty wild mammal (Ochotona curzoniae) corpses were placed on alpine meadow soil to study the carbon storage and carbon-fixing microbiota succession for a 94-day decomposition using next-generation sequencing. Our results revealed that 1) the concentration of total carbon increased approximately 2.24-11.22% in the corpse group. 2) Several carbon-fixing bacterial species (Calothrix parietina, Ancylobacter rudongensis, Rhodopseudomonas palustris) may predict the concentration of total carbon. 3) Animal cadaver degradation caused the differentiation of carbon-fixing microbiota structures during succession and made the medium-stage networks of carbon-fixing microbes more complicated. 4) The temporal turnover rate in the experimental groups was higher than that in the control groups, indicating a quick change of gravesoil carbon-fixing microbiota. 5) The deterministic process dominates the assembly mechanism of experimental groups (ranging from 53.42% to 94.94%), which reflects that the carbon-fixing microbial community in gravesoil can be regulated. Under global climate change, this study provides a new perspective for understanding the effects of wild animal carcass decay on soil carbon storage and carbon-fixing microbes.

Metagenomics reveals the self-recovery and risk of antibiotic resistomes during carcass decomposition of wild mammals.

Animal carcass decomposition may bring serious harm to the environment, including pathogenic viruses, toxic gases and metabolites, and antibiotic resistance genes (ARGs). However, how wild mammal corpses decomposition influence and change ARGs in the environment has less explored. Through metagenomics, 16S rRNA gene sequencing, and physicochemical analysis, this study explored the succession patterns, influencing factors, and assembly process of ARGs and mobile genetic elements (MGEs) in gravesoil during long-term corpse decomposition of wild mammals. Our results indicate that the ARG and MGE communities related to wildlife corpses exhibited a pattern of differentiation first and then convergence. Different from the farmed animals, the decomposition of wild animals first reduced the diversity of ARGs and MGEs, and then recovered to a level similar to that of the control group (untreated soil). ARGs and MGEs of the gravesoil are mainly affected by deterministic processes in different stages. MGEs and bacterial community are the two most important factors affecting ARGs in gravesoil. It is worth noting that the decomposition of wild animal carcasses enriched different high-risk ARGs at different stages (bacA, mecA and floR), which have co-occurrence patterns with opportunistic pathogens (Comamonas and Acinetobacter), thereby posing a great threat to public health. These results are of great significance for wildlife corpse management and environmental and ecological safety.

Copper and temperature shaped abundant and rare community assembly respectively in the Yellow River.

Untangling assembly and microbial interaction of abundant and rare microbiota in aquatic ecosystem is pivotal for understanding how community assembly respond to environmental variables and co-occurrence patterns. Here, we explored the assembly mechanisms, their drivers, and species co-occurrence of abundant and rare microbiomes in the Yellow River using 16S rRNA gene sequencing in Lanzhou, China. Here, abundant community was ubiquitous across all sites, whereas rare community was uneven distributed. The richness and community dissimilarity of rare taxa were significantly greater than those of abundant ones. Stochastic processes structured the rare community assembly in spring and winter, while deterministic processes shaped the abundant and rare community assembly in other seasons and all sites. Copper and water temperature mediated the balance between deterministic and stochastic processes of abundant and rare community, respectively. A few abundant taxa with closer relationships frequently occupied central positions and had a great effect on other co-occurrences in the network, while the majority of keystone microbiota were rare microbiome and played a considerable part in maintaining the network structure. Our study provides some ecological proposals for water quality management and ecological stability of the Yellow River. KEY POINTS: • Deterministic process dominated abundant and rare community assembly. • Cu and TW mediated the balance of abundant and rare community assembly respectively. • Abundant taxa had a greater effect on other co-occurrences in the network.

Deterministic Processes Shape Abundant and Rare Bacterial Communities in Drinking Water.

The deep mechanisms shaping bacterial assembly are a crucial challenge in drinking water ecosystem. However, much less is known about seasonal diversity distributions and assembly mechanisms of abundant and rare bacteria in drinking water. The combination of environmental variables and high-throughput 16S rRNA gene sequencing was conducted to examine the composition, assembly, co-occurrence patterns of abundant and rare bacteria from five drinking water sites across four seasons in one year in China. The results indicated that abundant taxa were mainly composed of Rhizobiales_UG1, Sphingomonadales_UG1, and Comamonadaceae, while rare taxa were Sphingomonadales_UG1, Rhizobiales_UG2, and Rhizobiales_UG1. The richness of rare bacteria was greater than that of abundant ones, and the richness had no differences among seasons. The beta diversity was significantly discrepant in abundant and rare communities and among seasons. Deterministic mechanism accounted for a larger contribution to abundant taxa than rare taxa. Furthermore, water temperature had higher effects on abundant microbiome than rare ones. Co-occurrence network analysis indicated that abundant taxa that occupied frequently in central positions had stronger effect on co-occurrence network. In our study, these results collectively suggested that rare bacteria respond to environmental variables with an analogical pattern to abundant counterparts (similar community assembly), but their ecological diversities, driving forces, and co-occurrence patterns were not equivalent in drinking water.

A pan-cancer analysis of molecular characteristics and oncogenic role of gasdermins.

BACKGROUND: The gasdermins (GSDMs) family is proposed to be pore-forming effector proteins that cause cell membrane permeabilization and pyroptosis. Despite our increasing knowledge of GSDMD, GSDME and GSDMB, the biological functions and the regulation of GSDM expression and activation remain elusive for most GSDMs. In this study, we analyzed the molecular characteristics and oncogenic role of GSDM family genes systematically. METHODS: TCGA, CCLE, cBioPortal, GEPIA, CellMiner and BioGRID databases were utilized in this study. Immunohistochemical analysis and a series of in vitro experiments were conducted. RESULTS: We found that, in cancer, GSDM genes and their expressions extensively changed, which were associated with patient survival. The expression of GSDMs was widely associated with cancer-related pathways, drug resistance, immune subtypes, tumor microenvironment and cancer cell stemness. However, an intra- and inter-cancer heterogeneity was discovered regarding the corresponding GSDM gene. We found that GSDMA and GSDMB regulated drug resistance to the opposite direction of GSDME. In colorectal cancer, GSDME might be a positive regulator in cell invasion and metastasis through cell migration and angiogenesis, while GSDMA, GSDMB and GSDMD might be a negatively regulator of cell migration. CONCLUSIONS: GSDM family genes might play important roles in cancer other than pyroptosis. We suggest more efforts be made to investigate the GSDM family and each GSDM gene be studied as an entity in each type of cancer.

Epithelial-mesenchymal Transition of Peritoneal Mesothelial Cells Is Enhanced by M2c Macrophage Polarization.

BACKGROUND: Peritoneal fibrosis (PF) can reduce the efficiency of peritoneal dialysis and eventually lead to ultrafiltration failure. Epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is the start of PF. Macrophages are involved in the process. This study was to investigate the effect of macrophage polarization on EMT of PMCs. METHODS: Monocyte-macrophage cells (THP-1) were treated to induce macrophage subsets (M1, M2a, M2c). The inducing was assessed by detecting protein and mRNA expression of cytokines using ELISA and RT-PCR. Subsequently, PMCs were co-cultured with M1, M2a and M2c, respectively, in Transwell chambers for 48 h and then expressions of E-cadherin and α-SMA were determined in PMCs. The PMCs that were not co-cultured with macrophages served as control PMCs. One-way ANOVA and SNK-q test were used to conduct statistics and P < .05 as significant. RESULTS: Detection of the cytokines, including IL-6, IL-10, IL-12, TGF-ß1, CCL17 and CXCL13, verified that the inducting of macrophage subtypes was successful. Compared to control, E-cadherin protein expression was significantly decreased and α-SMA protein expression increased in M1-treated PMCs (P < .05); M2a-treated PMCs had an increased gene expression of α-SMA (P < .05); E-cadherin protein and gene expression were decreased and α-SMA protein and gene expression increased significantly in M2c-treated PMCs (P < .05 or P < .01). CONCLUSIONS: EMT of PMCs is enhanced by M2c macrophage polarization; meanwhile, M1 and M2a polarization may have the effect to some extent, but not as definite as M2c.

Corpse decay of wild animals leads to the divergent succession of nrfA-type microbial communities.

Animal carcasses introduce large amounts of nitrates and ammonium into the soil ecosystem. Some of this ammonium is transformed from nitrite through the nrfA-type microbial community. However, it is unclear how nrfA-type microorganisms respond to the decomposition of corpses. This study applied high-throughput sequencing to characterize the ecological succession of nrfA-type microbial communities in grassland soil. Our results showed that Cyclobacterium and Trueperella were the predominant genera for nrfA-type communities in soil with a decomposing corpse (experimental group), while Cyclobacterium and Archangium were dominant in soil without a corpse (control group). The alpha diversity indexes and the resistance and resilience indexes of the microbial communities initially increased and then decreased during decomposition. Compared with the control group, nrfA-encoding community structure in the experimental group gradually became divergent with succession and temporal turnover accelerated. Network analysis revealed that the microbial communities of the experimental group had more complex interactions than those of the control groups. Moreover, the bacterial community assembly in the experimental group was governed by stochastic processes, and the communities of the experimental group had a weaker dispersal capacity than those of the control group. Our results reveal the succession patterns of the nrfA-type microbial communities during degradation of wild animal corpses, which can offer references for demonstrating the ecological mechanism underlying the changes in the nrfA-type microbial community during carcass decay. KEY POINTS: • Corpse decay accelerates the temporal turnover of the nrfA-type community in soil. • Corpse decay changes the ecological succession of the nrfA-type community in soil. • Corpse decay leads to a complex co-occurrence pattern of the nrfA-type community in soil.

Corpse decomposition of freshwater economic fish leads to similar resistomes and the enrichment of high-risk antibiotic resistance genes in different water types.

Animal carcass decay produces many poisonous metabolites and chemical pollutants, which pose potential ecological risks to the aquatic environment and human health. However, the effects of animal cadaver decomposition on high-risk antibiotic resistance genes (ARGs) and potential pathogens in different water types are still unknown. In this study, fifteen freshwater economic fish (Carassius auratus) corpses were put into three types of water (i.e., pond water, tap water, and domestic sewage) for a 100-day decomposition. Next generation sequencing and HT-qPCR were used to illustrate how corpse decomposition affected microbial communities and ARG profiles. Our results revealed that fish corpse degradation caused similar resistomes and microbiome in different water types. MLSB (Macrolide-Lincosamide-Streptogramin B), ß-lactamase, sulfonamide, tetracycline resistance genes and transposase genes in the experimental groups were increased. Among them, tetracycline resistance genes were enriched by 224 to 136,218-fold during the process of corpse degradation. Furthermore, high-risk ARGs (ermB, floR and dfrA1), which resist to MLSB, multidrug and sulfonamide respectively, were significantly enriched in the cadaver groups and had co-occurrence patterns with opportunistic pathogens, such as Bacteroidetes, which was more than 37 times in carcass groups than that in control groups. The study is able to draw a general conclusion that cadaver decomposition of freshwater economic fish deteriorates the aquatic environment by affecting high-risk ARGs and pathogenic microorganisms regardless of water types, which poses potential threats to human health. Therefore, timely management and treatment of animal carcasses is of great significance to the protection of water environment.

Nationality and body location alter human skin microbiome.

Skin microbiomes function directly in human health and are affected by various external and internal factors. However, few studies have showed the variation of human skin microbiota at multiple body sites in individuals of different national origin living in the same environment. Here, using 16S rRNA sequencing, we investigated the diversity and function of skin microbiomes in different body locations of Chinese and Pakistani individuals from a single college in China. Body location and nationality significantly affected community structures, while season and gender only impacted community member. Due to different lifestyles and likely genetic characteristics of the hosts, Proteobacteria was more abundant in Pakistanis than in Chinese individuals. There were significant differences in the Shannon diversity of skin microorganisms among different skin sites of Chinese individuals, but not in Pakistanis. PICRUSt prediction indicated that gene functions involved in carbohydrate metabolism, lipid metabolism, and xenobiotics biodegradation and metabolism were higher in bacteria collected from Pakistanis than those from Chinese individuals, but the amino acid metabolism of skin microorganisms in Chinese people was higher. The relative abundances of potential pathogenic bacteria also differed in different body locations, providing a foundation for studying skin-associated bacterial diseases. Through a meta-analysis of 233 human skin samples from eight elevational sites in western China, we found that skin microbial diversity first decreased and then increased with increasing altitude. Network analysis showed positive correlation between altitude and Lactobacillus, Chryseobacterium, or Acinetobacter. Our results uncover the variation of human skin microbiota allowing future explorations of potential significance for human health. KEY POINTS: • Body location and nationality affect skin microbiota diversity and function. • Proteobacteria was more abundant in Pakistanis than in Chinese. • Skin microbial diversity first decreased and then increased with elevated altitude.

TAZ-regulated expression of IL-8 is involved in chemoresistance of hepatocellular carcinoma cells.

Chemotherapy resistance is one of the major challenges for the treatment of hepatocellular carcinoma (HCC). In order to investigate the mechanisms involved in chemoresistance of HCC, we established cisplatin (CDDP) and doxorubicin (Dox) resistant HCC cells. The expression of transcriptional coactivator with PDZ-binding motif (TAZ), one of the major downstream effectors of Hippo pathway, was upregulated in chemoresistant HCC cells. Targeted inhibition of TAZ via its siRNAs can restore CDDP and Dox sensitivity of chemoresistant HCC cells. The upregulation of TAZ increased the expression of IL-8 in HCC/CDDP and HCC/Dox cells. Recombinant IL-8 (rIL-8) antagonized the increased chemosensitivity mediated by TAZ knockdown. Mechanistically, TAZ can directly bind with the promoter of IL-8 to activate its transcription in chemoresistant HCC cells. Collectively, our data showed that TAZ-regulated expression of IL-8 was involved in chemoresistance of HCC cells. It indicated that targeted inhibition of TAZ/IL-8 axis might be helpful to improve chemotherapy efficiency for HCC.

Multichannel-Structured Three-Dimensional Chip for Highly Sensitive Pathogenic Bacteria Detection Based on Fast DNA-Programmed Signal Polymerization.

The threat of food safety and the limited analytical methods with high performance promote the growing interest in the development of pathogenic bacteria biosensors. This study presents a pathogenic bacteria biosensing system, where a novel three-dimensional (3D) chip acts as an analytical carrier and DNA-programmed hybridization chain reaction (HCR) causes signal amplification. The 3D chip is designed featuring a compact multichannel structure. It has a large surface area for sensitive sensing and exhibits multiple functions of target capture, separation, rinsing, and signal detection to simplify the analysis processes. HCR, which enables the fluorophore's polymerization, is designed as two signal amplification modes, each with unique advantages. Mode I achieves highly sensitive detection in a "sandwich" assay format, in which a long HCR-amplified probe is used to boost the fluorescence signal. In mode II, the assembly of HCR is performed on the inner surface of the 3D chip. Especially, a group of rapid-assembly HCR sequences is proposed, of which the assembly time as short as 15 min stands out among the related works previously reported. Under the optimal conditions, the proposed biosensing system has the limits of detection (LOD) of 4 and 8 cfu/mL in mode I for Staphylococcus aureus detection and in mode II for Salmonella enterica Typhimurium detection, respectively. The specificity and the real sample applications are evaluated. This multichannel-structured 3D chip based on HCR signal amplification has potential applications in food safety monitoring and biosensor development.

Rs1520220 and Rs2195239 Polymorphisms of IGF-1 Gene Associated with Histopathological Grades in IgA Nephropathy in Northwestern Chinese Han Population.

BACKGROUND/AIMS: Insulin-like growth factor-1 (IGF-1) plays important roles in cellular proliferation, differentiation, and growth. Previous studies showed that single-nucleotide polymorphisms (SNPs) of IGF-1 are associated with various diseases. This case-control study aimed to examine the relationship between IGF-1 polymorphisms and IgA nephropathy (IgAN) risk in a Chinese Han population. METHODS: We recruited 351 IgAN patients and 310 healthy controls from Northwestern China. Sequenom MassARRAY was utilized to examine the genotypes of two common IGF-1 SNPs (rs1520220 and rs2195239). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by the Chi square test to evaluate the associations between IGF-1 and IgAN. RESULTS: Our study demonstrated that IGF-1 gene rs1520220 and rs2195239 polymorphisms did not confer susceptibility to IgAN. We found no correlation between gender, blood pressure, proteinuria, eGFR, and IgAN in both SNPs. However, the rs1520220 and rs2195239 variants were correlated with M1 and E1 in patients with IgAN (M0/M1: CC vs. CG+GG: OR = 1.62, P = 0.04; E0/E1: CC vs. CG+GG: OR = 1.95, P = 0.004; GG vs. GC+CC: OR = 1.90, P = 0.004, respectively). CONCLUSION: These results indicate that IGF-1 gene polymorphisms play crucial roles in the histopathological progression of IgAN in the Chinese Han population.

The Endothelial Nitric Oxide Synthase Gene Polymorphism is Associated with the Susceptibility to Immunoglobulin a Nephropathy in Chinese Population.

BACKGROUND/AIMS: Endothelial nitric oxide synthase (eNOS) is one of the most important enzymes for producting nitric oxide (NO), which regulate the function of many organs and cells. The single nucleotide polymorphisms (SNPs) of eNOS were found to be associated with many kidney diseases. However, it is lack of relevant studies to evaluate the associations between eNOS polymorphisms and immunoglobulin A nephropathy (IgAN). This case-control study aimed to evaluate the relationship between eNOS polymorphisms and IgAN. METHODS: We recruited 351 IgAN patients and 310 age- and sex-matched healthy controls from Northwest China. Sequenom MassARRAY was used to detect the genotypes of two common eNOS SNPs (rs1799983 and rs2070744). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by the Chi square test to evaluate the associations between eNOS and IgAN. Phase 2.1 was used to conduct haplotype analysis. RESULTS: In the overall analysis, we found that the rs1799983 polymorphism was associated with a decreased risk of IgAN (G/T vs. G/G: OR=0.57, 95%CI=0.34-0.96; G/T+T/T vs. G/G: OR=0.52, 95%CI=0.31-0.86; G/T vs. G/G-T/T: OR=0.60, 95%CI=0.36-0.99; Log-additive model: OR=0.48, 95%CI=0.30-0.78). Haplotype analysis indicated that Trs1799983Crs2070744 is a protective factor against IgAN (OR=0.62, 95%CI=0.42--0.92). However, no significant differences were found between the two SNPs (rs1799983 and rs2070744) and clinical features (age, sex, blood pressure, and Lee's grade) of IgAN. CONCLUSION: The eNOS gene rs1799983 polymorphism and Trs1799983Crs2070744 haplotype may reduce the risk of IgAN in Chinese populations.

Association of Interleukin-10 Polymorphisms (rs1800872, rs1800871, and rs1800896) with Predisposition to IgA Nephropathy in a Chinese Han Population: A Case-Control Study.

BACKGROUND/AIMS: IgA nephropathy (IgAN) is a common form of primary glomerulonephritis worldwide. Previous studies indicated that IL-10 single nucleotide polymorphisms (SNP) play an important role in IgAN pathogenesis, but the results were controversy. This study aimed to investigate the association between IL-10 SNPs (rs1800872, rs1800871, and rs1800896) with IgAN in a Chinese Han population. METHODS: We conducted a case-control study that included 351 patients with IgAN and 310 age-, gender- and ethnicity-matched healthy controls. Three promoter SNPs (rs1800872, rs1800871, and rs1800896) of IL-10 were genotyped by Sequenom MassARRAY. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the relationship with IgAN. RESULTS: We found that the rs1800896 did not correlate with IgAN risk, whereas rs1800872 and rs1800871 were significantly associated with increased IgAN risk in all genetic models. The haplotype analysis indicated that the CCA haplotype was associated with increased IgAN risk (OR = 1.36; 95% CI = 1.05-1.75). Moreover, there were no associations between these SNPs and blood pressure or gender, whereas the rs1800896 variant was correlated with higher 24-hour urine protein in patients with IgAN. CONCLUSION: Taken together, these results suggest that IL-10 is a susceptibility gene in patients with IgAN.

Association Between IFN-γ Gene Polymorphisms and IgA Nephropathy in a Chinese Han Population.

BACKGROUND/AIMS: IFN-γ was reported to be involved in the development and progression of Immunoglobulin A nephropathy (IgAN), however, few studies have investigated the association between IFN-γ polymorphisms and IgAN. Therefore, we performed a case-control study to assess the association between IFN-γ polymorphisms and the risk of IgAN. METHODS: Sequenom MassARRAY was used to genotype two SNPs (rs1861494 and rs2430561) in 351 patients with IgAN and 310 healthy controls. Associations were evaluated as odd ratios (OR) with 95% confidence intervals (CI). RESULTS: No association was found between IFN-γ rs1861494 and IgAN risk or clinical parameters. For rs2430561, the AA genotype was more common in patients with IgAN, compared with controls (AT vs. AA: OR = 0.57, P = 0.035). IFN-γ-rs2430561 T allele may be a protective factor for IgAN susceptibility (T vs. A: OR = 0.59, P = 0.04). Subgroup analysis based on clinical features revealed no significant association between rs2430561 polymorphism and clinical data such as gender, 24-h urine protein, blood pressure, Oxford classifcation and estimated glomerular fltration rate. IgAN patients had a higher IFN-γ serum level than healthy controls and patients with rs1861494 AA genotype had a higher IFN-γ serum level compared with those with AG/GG genotypes. CONCLUSIONS: IFN-γ polymorphisms may be involved in the development and progression of IgAN.