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Lei Cheng

Publications and source records attributed to Lei Cheng.

At least 19 recordsLinked to original sources
PubMed2026

Circadian reprogramming of inflammation and metabolism in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is driven by inflammation, fibrosis, and metabolic dysfunction. While circadian rhythm dysregulation is well documented in chronic disorders, its specific impact on CKD pathogenesis remains elusive. METHODS: We performed four-hour interval time-series RNA sequencing on renal tissues from control and CKD mice. We used the JTK_CYCLE algorithm to identify rhythmic genes and categorize them as lost, acquired, or sustained in CKD; we subsequently performed focused bioinformatic analyses. RESULTS: The renal circadian profile was substantially altered; acquired rhythmicity emerged as the dominant pattern, and core clock gene expression was disrupted. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that upregulated acquired-rhythmic genes in CKD were enriched in immune-inflammatory pathways; the expression of these genes peaked at Zeitgeber time (ZT) 12-16, consistent with a higher level of renal macrophage infiltration at ZT16 than at ZT0. Conversely, genes associated with nutrient and energy metabolism pathways were downregulated but acquired rhythmicity in CKD. Dapagliflozin improved renal function and restored the circadian expression rhythms of NR1D1 and p-BMAL1. CONCLUSIONS: CKD profoundly remodels the renal circadian transcriptome, driving immune-inflammatory and metabolic pathways into maladaptive rhythmicity. Furthermore, dapagliflozin can partially restore the expression of renal core clock genes.

Animals↗
PubMed2026

An integrated global resource of wetland microbiomes linking environmental metadata, community profiles, and genome-resolved metabolic traits.

Wetlands are biogeochemical hotspots pivotal to global carbon and nutrient cycling, yet genome-resolved studies across diverse wetland types remain limited. To address this, we constructed a global wetland metagenomic dataset, integrating environmental metadata, community profiles, and genome-resolved metabolic traits. This dataset comprises 1,962 samples-including 129 newly sequenced field-collected samples-from lakes, rivers, paddies, marshes, and coastal wetlands, spanning water, soil, and sediment habitats. We generated comprehensive taxonomic profiles for all 1,962 samples, and used 251 samples to reconstruct 5,704 sample-specific metagenome-assembled genomes (MAGs). These MAGs were subsequently dereplicated to establish a normalized, non-redundant catalog of 4,164 representative genomes. We further mapped gene repertoires to 549 KEGG modules to decode the metabolic potential of all 5,704 MAGs. This dataset depicts an overview of microbial genomic diversity across global wetlands and provides a comprehensive resource for understanding the metabolic capabilities, ecology, and evolution of wetland microbiomes.

Wetlands↗
PubMed2026

Multi-omics dynamic profiling reveals predictive biomarkers for first-line immunochemotherapy in extensive-stage small-cell lung cancer.

BACKGROUND: Extensive-stage small-cell lung cancer (ES-SCLC) is associated with a poor prognosis. Although first-line immunochemotherapy improves clinical outcomes, robust prognostic biomarkers for this treatment modality remain unavailable. The aim of this study was to identify non-invasive, easily accessible, and dynamically monitored biomarkers of ES-SCLC by machine learning integrating serum metabolomics, lipidomics, and proteomics at multiple time points. METHODS: A total of 816 serum samples were collected from ES-SCLC patients receiving first-line immunotherapy combined with chemotherapy or first-line chemotherapy for metabolomics, lipidomics, and proteomics analysis. The immunochemotherapy cohort was randomly divided into training and validation subsets at a 6:4 ratio. Biomarkers were identified using machine learning algorithms, and their prognostic significance was evaluated through receiver operating characteristic (ROC) analysis, Kaplan–Meier survival analysis, and multivariate Cox regression. Potential metabolic pathways and mechanisms were further explored via integrated multi-omic analysis. RESULTS: The immunochemotherapy exhibited a prolonged median progression-free survival (PFS) and higher objective response rate (ORR) compared to the chemotherapy group. A total of 5 serum metabolites (uric acid, L-aspartate-semialdehyde, dimethisterone, xanthine, L-cysteine), 6 lipids (Cer d18:1/26:0, Cer d18:2/25:0, SM d18:1/20:1, SM d17:1/25:1, DG O-18:1_16:0, PS 18:0_24:0), and 3 proteins (ACIN1, ACSL4, PHGDH) were identified and constructed into independent prognostic models. Among patients receiving immunochemotherapy, those categorized as low-risk based on the model demonstrated significantly longer PFS compared with those in the high-risk group. These prognostic signatures also retained predictive value in patients who underwent second-line treatment with anlotinib plus immunochemotherapy. Integrated analysis revealed that glycine, serine, and threonine metabolism was the commonly enriched pathway across all three omics layers. Notably, PHGDH (protein), L-aspartate-semialdehyde and L-cysteine (metabolites), and PS (18:0_24:0) (lipid), key elements in this pathway, were all incorporated in the predictive model. In addition, models of the composition of these substances after one cycle of treatment can still predict the prognosis of patients. CONCLUSION: In this study, we constructed and validated a set of non-invasive, dynamically monitorable prognostic models (containing 5 metabolites, 6 lipids, and 3 proteins) using machine learning by integrating multiple time point data from the serum metabolome, lipid panel, and proteome to accurately distinguish the prognostic risk of patients with ES-SCLC receiving immunochemotherapy. PFS was significantly prolonged in patients in the low-risk group, and this model remains predictive in the subsequent second-line treatment with anlotinib in combination with immunochemotherapy. Glycine-serine-threonine metabolic pathway may be the key mechanism, of which PHGDH, L-aspartate semialdehyde, L-cysteine and PS (18:0_24:0) are the core predictors. This study provides the first multi-omics dynamic prognostic tool for ES-SCLC immunochemotherapy and reveals potential therapeutic targets.

Humans↗
PubMed2025

COL5A1 in the tumor microenvironment predicts the prognosis of head and neck cancer.

ObjectivesThis study aims to investigate the significance of tumor microenvironment (TME)-related genes and signal transduction pathways in head and neck cancer (HNC).MethodsGene expression and clinical data of HNC patients were obtained from the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were screened through a multi-step filtration approach to obtain candidate predictors. The biological role of COL5A1 in HNC was verified through rigorous bioinformatic analysis, experimental validation using quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) analysis from HNC samples, and IHC data from the Human Protein Atlas (HPA) database.ResultsCOL5A1 was significantly upregulated in HNC tissues and cell lines. High COL5A1 expression was significantly associated with advanced tumor grade (P&#x2009;<&#x2009;.05) and shorter survival (TCGA: P&#x2009;<&#x2009;.001; GSE42743: P&#x2009;=&#x2009;.004). COL5A1 was an independent prognostic indicator (univariate analysis: HR&#x2009;=&#x2009;1.324, P&#x2009;=&#x2009;.001; Multivariate analysis: HR&#x2009;=&#x2009;1.326, P&#x2009;=&#x2009;.005). It was enriched in pathways related to tumor invasion and immune responses, and its expression was associated with decreased levels of CD8+ T cells and increased levels of macrophages and neutrophils. Spatial distribution analysis revealed higher expression at the tumor's leading edge (vs. tumor core: P&#x2009;<&#x2009;.001). COL5A1 expression is associated with tumor stage, with more pronounced expression in advanced-stage tumors.ConclusionCOL5A1 represented a novel potential prognostic indicator and therapeutic target in an HNC database sample, as its expression is closely linked to tumor progression, immune cell infiltration, and adverse clinical outcomes. These findings, primarily derived from squamous cell carcinoma-dominated cohorts, warrant further functional validation.

Humans↗
PubMed2006

A simple method for the estimation of peritoneal fluid transport.

BACKGROUND: Evaluating peritoneal fluid kinetics is of great value to the adjustment of peritoneal dialysis prescription. Therefore, in the present study, we developed a simple method, based on a membrane transport model, to evaluate the fluid transport characteristics of the peritoneal membrane in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Patients' peritoneal ultrafiltration (UF) volume was collected for 2 consecutive months. Membrane transport model and nonlinear least-squares regression analyses were applied to the pooled UF volume for the first month for fluid kinetic simulation and the data from the second month were used to evaluate the reliability and precision of simulated UF values. RESULTS: Seventeen chronic peritoneal dialysis (PD) patients were selected for the present study. Simulated UF values based on the pooled UF volume in the first month correlated significantly with the actual measured UF values in the second month. By Bland-Atman plot, the width between the 95% limits of agreement fell within -133.3 to 154.2 ml with a mean difference of 10.5 ml. CONCLUSION: Our study showed that applying the fluid transport model and nonlinear least-squares regression analysis to the pooled actual UF value might be a good and simple way to predict peritoneal UF.

Aged↗
PubMed2006

The dual actions of angiogenesis and anti-apoptosis induced by an isolated fraction from Geum japonicum repair muscle ischemia.

The fundamental improvement of muscle ischemia requires the re-establishment of sufficient vessel network. Despite many kinds of drugs have been used for ischemia, effective angiogenic drug is very limited. Here, we reported the identification and isolation of a potent angiogenic fraction (angio-T) from Geum japonicum and assessment of its therapeutic effects on muscle ischemia by reconstituting the insufficient blood supply network and enhancing cell survival potential. It was demonstrated that angio-T not only significantly enhanced the proliferation of cultured HCAECs in vitro, but also significantly enhanced the survival potential of the myofibers at risk and neovascularization in ischemic muscles leading to reconstitution of these vessel networks, significant reduction of ischemic areas, and significant myofiber regeneration in ischemic area one week post-ischemia.

Animals↗
PubMed2006

Repair of infarcted myocardium by an extract of Geum japonicum with dual effects on angiogenesis and myogenesis.

BACKGROUND: It has become apparent recently that cardiac myocytes can divide after myocardial infarction, a circumstance that challenges the orthodox view that myocytes may be terminally differentiated. Replacement of the necrosed heart tissue by newly regenerated functional myocardium is a therapeutic ideal, but attempts to reconstitute functional myocardia and coronary vessels have been less successful. METHODS: We isolated a fraction containing 5 compounds from the Chinese herb Geum japonicum, which stimulates the processes of angiogenesis and cardiomyogenesis. We investigated these dual properties in both ex vivo and in vivo systems. RESULTS: We observed that this bioactive fraction displayed favorable dual actions on early angiogenesis and cardiomyogenesis in acute myocardial infarction in an animal model. Our results demonstrated that application of this bioactive fraction showed pronounced effects on limiting infarct size by 35%-45%, stimulating early development of new blood vessels in 24 h, and regenerating myocardium, replacing approximately 49% of the total infarction volume after 2 weeks. Echocardiographic studies demonstrated marked improvement of left ventricular function within 2 days after infarction, and the improvement was sustained for >1 month. CONCLUSIONS: The properties of this bioactive fraction appear to be entirely novel and represent a new approach for the treatment of ischemic heart disease.

Animals↗
PubMed2006

[Preliminary study of serum proteome biomarkers of hypopharyngeal squamous cell carcinoma].

OBJECTIVE: To screen the serum proteome biomarkers of hypopharyngeal squamous cell carcinoma (HSCC) and to establish a predictive model for early detection of HSCC. METHODS: Serum samples were collected from 48 HSCC patients before surgery and 52 age and sex-matched individuals without cancer used as controls. The samples were divided into 2 sets: training set (including 36 HSCC patients and 36 controls) and blind testing set (including 12 HSCC patients and 16 controls). With WCX2 and IMAC3 protein chips, surface-enhanced laser desorption/ionization (SELDI) was used to analyze the serum protein profiling. 72 samples of the training set were analyzed by a decision tree algorithm to be able to differentiate HSCC patients from controls. Double-blind test was used to determine the sensitivity and specificity of the classification model. RESULTS: Ranging from 2000 - 50000 (M/Z), 11 potential biomarkers on WCX2 and 19 biomarkers on IMAC3 protein chip could differentiate HSCC patients from the control set (P < 10(-5)). Among them 4 candidate protein peaks with the m/z values of 7796, 4216, 5927, and 5361 were selected to be used to establish a predictive model by Biomarker Pattern Software. The model separated effectively the HSCC samples from the control samples, achieving a sensitivity of 94.44%, and a specificity of 88.89%. An accuracy of 85.71% (24/28), sensitivity of 91.67% (11/12), specificity of 81.25% (13/16), positive predictive value of 78.57%% (11/14), and negative predictive value of 92.85% (13/14) were validated in the double-blind testing set. CONCLUSION: The SELDI-TOF-MS Protein Chip combined with artificial intelligence classification algorithm helps find serum proteome biomarkers and establish predictive model for early diagnosis of HSCC. This technique has potential for the development of a screening test for the detection of HSCC.

Adult↗
PubMed2006

Interconverting conformations of variants of the human amyloidogenic protein beta2-microglobulin quantitatively characterized by dynamic capillary electrophoresis and computer simulation.

Capillary electrophoretic separation profiles of cleaved variants of beta2-microglobulin (beta2m) reflect the conformational equilibria existing in solutions of these proteins. The characterization of these equilibria is of interest since beta2m is responsible for amyloid formation in dialysis-related amyloidosis and thus is able to attain alternative conformations that lead to irreversible aggregation and precipitation. In this study, we quantitate the increased conformational instability of cleaved beta2m by extracting rate constants and activation energies by simulating the experimental data using a unified theory for dynamic chromatography and dynamic electrophoresis. The results are correlated with the outcome of independent experiments based on mass spectrometric measurement of H/D exchange. This study illustrates that dynamic capillary electrophoresis is suitable for the investigation of the interconversion of protein conformations of amyloidogenic molecules and is not only restricted to ideal model compounds.

Amyloid↗
PubMed2006

A new function of a previously isolated compound that stimulates activation and differentiation of myogenic precursor cells leading to efficient myofiber regeneration and muscle repair.

Muscle repair following severe injury is slow and incomplete due to the limited regenerative capacity of muscles comprising the function. In this study, one pure compound structurally corresponding to triterpenoid, which can directly induce the activation, proliferation and maturation of quiescent satellite cells into myocytes in vitro, was isolated from Geum japonicum. The potential effect of this compound on myogenesis was further tested in repair of severe muscle injury. It was found that this compound could significantly stimulate the regenerative potential of the damaged muscle resulting in regeneration of myotubes and myotube bundles time-dependently replacing the damaged muscle tissues. This compound-mediated active regeneration of new myofibers repairing damaged muscles was probably due to its direct action on activation and proliferation of quiescent myogenic precursor cells and enhancement of their maturation into regenerating myotubes, as was demonstrated in our primary myogenic precursor cells culture experiments. The up-regulated expression of endogenous phospho-Akt1 in compound-treated myogenic precursor cells may also contribute to the process of myofiber regeneration and muscle repair probably via promoting myogenic cell survival capacity.

Animals↗
PubMed2006

Detection of hypopharyngeal squamous cell carcinoma using serum proteomics.

CONCLUSIONS: The combination of surface-enhanced laser desorption/ionization (SELDI) with bioinformatics tools could help find serum proteome biomarkers and establish a predictive model for early detection of hypopharyngeal squamous cell carcinoma (HSCC). OBJECTIVES: Proteomic profiling of serum using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is an emerging technique to identify new biomarkers in biological fluids and to establish clinically useful diagnostic computational models. We used it to find new potential biomarkers and to establish a predictive model for early detection of HSCC. MATERIALS AND METHODS: One hundred serum samples including 48 from HSCC patients and 52 from normal controls which were divided into a training set and a blind testing set were treated on WCX2 and IMAC3 protein chip, and serum protein or peptide patterns were detected by SELDI-TOF-MS. The data of spectra were analyzed by Biomarker Wizard software to screen serum proteome biomarkers of HSCC. A decision tree classification algorithm and blind validation were determined by Biomarker Pattern Software (BPS). RESULTS: Ranging from 2 to 30 kDa, 45 potential biomarkers could differentiate HSCC patients from normal controls (p < 0.05). Among them four candidate protein peaks with m/z values of 7796, 4216, 5927, and 5361Da were selected to establish a predictive model by BPS with sensitivity of 94% and specificity of 89%. A sensitivity of 92% and specificity of 82% were validated in the blind testing set.

Adult↗
PubMed2006

P38 MAP-kinase pathway is involved in the production of CLC-3 in nasal epithelial cells with allergic rhinitis induced by interleukin-4.

OBJECTIVE: The objective of this study was to evaluate the role of p38 MAP-kinase (MAPK) pathway on CLC-3 expression after interleukin-4 (IL-4) induction in primary cultured human nasal epithelial cells (HNECs) from patients with allergic rhinitis (AR). METHODS: Cultured HNECs from five patients with AR were treated with IL-4 (20 ng/mL) with or without SB203580, a selective inhibitor of p38 MAPK, at different concentrations and durations. CLC-3 was detected in HNECs by immunohistochemistry and real-time quantitative reverse transcription-polymerase chain reaction. p38 MAPK and phosphorylated p38 MAPK (pp38 MAPK) was examined by Western blotting. RESULTS: After exposure to SB203580, CLC-3 expression induced by IL-4 was downregulated in HNECs in a concentration and time-dependent manner. This downregulation was associated with a decrease in pp38 MAPK. CONCLUSION: These results confirmed that IL-4 can induce CLC-3 production in HNECs with AR through a p38 MAPK-dependent pathway. Inhibitors of p38 MAPK may become an important strategy for the treatment of AR.

Adult↗
PubMed2006

Effect of antihistamine eye drops on the conjunctival provocation test with Japanese cedar pollen allergen.

BACKGROUND: Approximately 16.2% of the Japanese population suffer from cedar pollinosis, with various manifestations such as ophthalmic, laryngo-pharyngeal and skin symptoms in addition to nasal symptoms. Thus, the annual pollen season is an agonizing period for patients. No study has reported symptoms and their clinical courses after conjunctival provocation with purified cedar pollen allergen Cry j1 as well as suppression of these allergen-induced ocular symptoms by antihistamine eye drops. METHODS: Nine patients with Japanese cedar pollinosis who had no nasal or ocular symptoms were included in the present study, after obtaining informed consent in writing. 1) Purified cedar pollen allergen Cry j1 was instilled in the left eye and phosphate-buffered saline (PBS) in the right eye as a control. 2) Levocabastine hydrochloride ophthalmic suspension and ketotifen fumarate ophthalmic solution were respectively instilled in the left and right eyes, which were then challenged with the allergen. Ocular symptoms after provocation with the allergen were recorded through the clinical course. RESULTS: Pollen allergen-induced ocular symptoms were itching and hyperemia of the palpebral conjunctiva, and itching lasted for more than 5 hours. Moreover, preadministration of antihistamine eye drops suppressed the increases in the ocular symptom scores, eliminating itching within 1 hour. Allergen provoked not only ocular symptoms but also nasal symptoms in 77.8% of patients. CONCLUSIONS: Preadministration of antihistamine eye drops suppressed the symptoms induced by the allergen, which suggests that this is an effective early therapy for Japanese cedar pollinosis, if it is started before the pollen season. However, self-protection by patients using a mask may not be effective enough to suppress nasal symptoms during the pollen season, requiring them to additionally wear glasses to avoid exposure to the allergen.

Adult↗
PubMed2006

[Immunotherapeutic effects of beta-elemene combined with interleukin-23 gene-modified dendritic cells on murine pancreatic carcinoma].

BACKGROUND & OBJECTIVE: Dendritic cell (DC) vaccine is a kind of treatment vaccine with clinical application potency. Functional cytokines can enhance anti-tumor immune response of dendritic cells. This study was to investigate the protective effects on murine pancreatic carcinoma by beta-elemene combined with bone marrow-derived dendritic cells (BM-DCs) modified with murine interleukin (IL)-23 gene. METHODS: The murine IL-23 cDNA was sub-cloned into dual-expression vector. DCs were pulsed with tumor cell lysate after modified by IL-23 gene. Mice were injected with IL-23-transfected DC vaccine, non-transfected DC vaccine, and sodium, respectively. The immune preventative and immunotherapeutic effects of DC vaccines on mice and the cytokine release in vivo were assessed. Effects of vaccine combined with beta-elemene on tumor growth and survival period of the mice were observed. RESULTS: IL-23 protein apparently increased the antigen-presenting ability of DCs. After the vaccination of DC vaccines, IFN-gamma production in treatment group was significantly more than that of the control group (P<0.01), as well as, IL-4 production was less than that in the normal group (P<0.05). Tumor growth was obviously inhibited and the survival period of the mice was obviously prolonged in beta-elemene combined with DC vaccine group than in DC, beta-elemene, or control group (P<0.01). CONCLUSIONS: IL-23-modified DC vaccines can enhance specific Th1-type and CTL response against pancreatic carcinoma cells, induce not only preventative immunity, but also auto-immunity against pancreatic carcinoma. Moreover, beta-elemene has great collaborative anti-tumor function.

Animals↗
PubMed2006

[Articular cartilage defects repaired with homograft of mesenchymal stem cells seeded onto medical collagen membrane of guided tissue regeneration].

OBJECTIVE: To investigate the curative effects of homograft of the mesenchymal stem cells (MSCs) combined with the medical collagen membrane of the guided tissue regeneration(MCMG) on the full thickness defects of the articular cartilage. METHODS: MSCs derived from New Zealand rabbits aged 3-4 months weighing 2. 1-3.4 kg were cultured in vitro with a density of 5.5 x 10 (8)/ml and seeded onto MCMG. The MSC/MCMG complex was cultured for 48 h and transplanted into the full thickness defects on the in board condyle and trochlea. Twenty-seven healthy New Zealand rabbits were randomly divided into 3 groups of 9 rabbits in each. The cartilage defects in the in board condyle and trochlea were filled with the auto bone marrow MSCs and MCMG complex (MSCs/ MCMG) in Group A (Management A), with only MCMG in Group B (Management B) and with nothing in Group C (Management C). Three rabbits were killed at 4, 8 and 12 weeks after operation in each group, and the reparative tissue samples evaluated grossly,histologically and immunohistochemically were graded according to the gross and histological scale. RESULTS: Four weeks after transplantation, the cartilage and subchondral bone were regenerated in Group A; for 12 weeks, the regenerated cartilage gradually thicker; 12 week after transplantation, the defect was repaired and the structures of the articular surface and subchondral bone was.in integrity. The defects in Group A were repaired by the hyaline-like tissue and the defects in Groups B and C were repaired by the fibrous tissues. Glycosaminoglycan and type II collagen in Groups A, B and C were reduced gradually. The statistical analysis on the gross at 12 weeks and the histological gradings at 4 weeks, 8 weeks and 12 weeks showed that the in board condylar repair had no significant difference compared with the trochlearepair(P>0. 05). Management A was significantly better than Managements B and C (P<0. 05), and Management B was better than Management C (P<0. 05). CONCLUSION: Transplantation of the MSCs combined with MCMG on the full thickness defects of the articular cartilage is a promising approach to the the treatment of cartilage defects. MCMG can satisfy the demands of the scaffold for the tissue-engineered cartilage.

Animals↗
PubMed2005

Lack of association between the IL13 variant Arg110Gln and susceptibility to cedar pollinosis in a Japanese population.

BACKGROUND: Interleukin (IL)-13 has come to be appreciated as a molecule critically involved in allergic inflammatory responses. Recent studies revealed that a common variant in the coding region of the IL13 gene, Arg110Gln, has been implicated in the development of asthma and atopy. METHODS: To assess whether the IL13 variant Arg110Gln is associated with cedar pollinosis, one of the most common atopic diseases in the Japanese population, we examined the Arg110Gln variant using PCR-RFLP to compare the genotype and allele frequencies between 95 patients with cedar pollinosis and 95 healthy control subjects. Relationships between the Arg110Gln variant and the pollinosis-related traits, e.g. rhinitis severity, eosinophil counts in nasal secretion and serum total and allergen-specific IgE levels, were also investigated. RESULTS: The frequencies of the minor allele Gln110 were 25.8% in patients with cedar pollinosis and 30.9% in healthy control subjects (p > 0.05). There was also no significant difference in the genotype frequencies between cases and controls (p > 0.05). In addition, we found no significant association of the Arg110Gln variant with any of the pollinosis-related phenotypes (p > 0.05). CONCLUSIONS: Our data suggest lack of evidence for identifying the variant Arg110Glnat the IL13 locus as a genetic risk factor involved in the development of Japanese cedar pollinosis.

Arginine↗
PubMed2005

Functional haplotypes of IL-12B are associated with childhood atopic asthma.

BACKGROUND: IL-12 is a heterodimeric proinflammatory cytokine that forms a link between innate and adaptive immunity. Although associations between polymorphisms of IL-12B on chromosome 5q31-33 and asthma have been reported, the genetic influences of the polymorphisms and haplotype of IL-12B are unclear. OBJECTIVE: To examine whether polymorphisms in IL-12B are associated with childhood atopic asthma in a Japanese population. METHODS: We identified a total of 13 polymorphisms and characterized the linkage disequilibrium mapping of the gene. Three variants in the promoter and 3' untranslated region were genotyped, and we conducted case-control and case-only association studies between those variants and asthma-related phenotypes (childhood atopic asthma, n = 297; normal controls, n = 555). Haplotype association analysis and functional analysis of these variants were also performed. RESULTS: 3' Untranslated region 10841C > A was significantly associated with the risk of childhood atopic asthma (P = .00062). The -6415 promoter variant, in linkage disequilibrium with the 10841C > A (D' = 0.78 and r2 = 0.61), was also marginally associated with childhood atopic asthma (P = .051). We analyzed the 2-locus haplotype by using these 2 polymorphisms and found a positive association with haplotype CTCTAA-C (-6415 CTCTAA and 10841C; P = .00078). Furthermore, 10841C > A affects the stability of transcripts, and promoter variant -6415GC enhances the transcriptional level of IL-12B. CONCLUSION: Our results imply that functional haplotype CTCTAA-C, which affects the instability of transcripts and the lower transcriptional level of IL-12B, has a protective effect in childhood atopic asthma. On the basis of these findings, the IL-12B gene might be involved in the development of atopic asthma through functional genetic polymorphisms.

3' Untranslated Regions↗