The dehydration-responsive protein PpFAS1.3 in moss Physcomitrium patens plays a regulatory role in lipid metabolism.

Moss plants appear in the early stages of land colonization and possess varying degrees of dehydration tolerance. In this study, a protein called PpFAS1.3 was identified, which contains a fasciclin 1-like domain and is essential for the moss Physcomitrium patens' response to short-term rapid dehydration. When the FAS1.3 protein was knocked out, leafyshoots showed a significant decrease in tolerance to rapid dehydration, resulting in accelerated water loss and increased membrane leakage. Phylogenetic analysis suggests that PpFAS1.3 and its homologous proteins may have originated from bacteria and are specifically found in non-vascular plants like mosses and liverworts. As a dehydration-related protein, FAS1.3 plays a significant role in regulating lipid metabolism, particularly in the synthesis of free fatty acids (FFA) and the metabolism of two phospholipids, PC and PA. This discovery highlights the close connection between PpFAS1.3 and lipid metabolism, providing new insights into the molecular mechanisms underlying plant adaptation to stresses.

Management of Nontraumatic Spontaneous Renal Hemorrhage (Wünderlich Syndrome) through Robotic-Assisted Laparoscopic Nephrectomy: A Case Series.

BACKGROUND Wünderlich syndrome (WS) is a rare diagnosis of nontraumatic spontaneous renal hemorrhage into the subcapsular, perirenal, or pararenal spaces. Prompt and effective intervention is necessary for an accurate pathological diagnosis and preservation of life. In the current literature, open surgery is the primary option when conservative treatment fails, but there can be serious trauma and corresponding consequences. Herein, we present 3 cases of Wünderlich syndrome managed by robot-assisted laparoscopic nephrectomy via a retroperitoneal approach. CASE REPORT Patient 1 was a 44-year-old woman with right flank pain for 6 h. Patient 2 was a 53-year-old woman with a history of diabetes who had pain in her right flank pain and nausea for 1 day. Patient 3 was a 45-year-old man with left flank pain for 1 day. All cases of WS were confirmed by CT. All 3 patients were treated with retroperitoneal robot-assisted nephrectomy after conservative treatment failed. Pathological examination confirmed that patient 1 had angiomyolipoma, and patients 2 and 3 had renal clear cell carcinoma. At the 9-month follow-up, renal function was good and no evidence of recurrence or metastasis has been detected. CONCLUSIONS These cases have highlighted the importance of the clinical history and imaging findings in the diagnosis of Wünderlich syndrome, and show that rapid management can be achieved using robot-assisted laparoscopic nephrectomy. However, it is crucial to have a skilled surgical team and adequate preoperative preparation.

Morphological and Phylogenetic Characterization of Three Novel Thaxterogaster (Cortinariaceae) Species from China with an Emphasis on Their Subtropical Distribution.

Three new phlegmaciod species of Thaxterogaster, T. borealicremeolinus, T. rufopurpureus, and T. sinopurpurascens spp. nov., from subtropical China were described based on their morphological characteristics and molecular data. Thaxterogaster borealicremeolinus belongs to the sect. Cremeolinae and differs from the other species in this section in its larger basidiospores and its habitat in the Northern Hemisphere associated with Quercus sp. trees. Thaxterogaster rufopurpureus and T. sinopurpurascens belong to sect. Purpurascentes, in which T. rufopurpureus is characterized by a pileus with a reddish-brown coloration when mature and a clavate stipe, while T. sinopurpurascens is characterized by a violet basidiomata, except for a greyish orange to brown pileus, the distinctly marginate bulb of its stipe, and its distribution in subtropical China. The phylogenetic analyses were performed based on nrITS, and detailed descriptions of the new species are provided herein.

Asymmetric Divergent Synthesis of ent-Kaurane-, ent-Atisane-, ent-Beyerane-, ent-Trachylobane-, and ent-Gibberellane-type Diterpenoids.

A unified strategy toward asymmetric divergent syntheses of nine C8-ethano-bridged diterpenoids A1-A9 (candol A, powerol, sicanadiol, epi-candol A, atisirene, ent-atisan-16α-ol, 4-decarboxy-4-methyl-GA12, trachinol, and ent-beyerane) has been developed based on late-stage transformations of common synthons having ent-kaurane and ent-trachylobane cores. The expeditious assembly of crucial advanced ent-kaurane- and ent-trachylobane-type building blocks is strategically explored through a regioselective and diastereoselective Fe-mediated hydrogen atom transfer (HAT) 6-exo-trig cyclization of the alkene/enone and 3-exo-trig cyclization of the alkene/ketone, showing the multi-reactivity of densely functionalized polycyclic substrates with πC═C and πC═O systems in HAT-initiated reactions. Following the rapid construction of five major structural skeletons (ent-kaurane-, ent-atisane-, ent-beyerane-, ent-trachylobane-, and ent-gibberellane-type), nine C8-ethano-bridged diterpenoids A1-A9 could be accessed in the longest linear 8 to 11 steps starting from readily available chiral γ-cyclogeraniol 1 and known chiral γ-substituted cyclohexenone 2, in which enantioselective total syntheses of candol A (A1, 8 steps), powerol (A2, 9 steps), sicanadiol (A3, 10 steps), epi-candol A (A4, 8 steps), ent-atisan-16α-ol (A6, 11 steps), and trachinol (A8, 10 steps) are achieved for the first time.

Estimating the effects of crime maps on house prices using an (Un)natural experiment: A study protocol.

Street-level crime maps are publicly available online in England and Wales. However, there was initial resistance to the publication of such fine-grained crime statistics, which can lower house prices and increase insurance premiums in high crime neighbourhoods. Identifying the causal effect of public crime statistics is difficult since crime statistics generally mirror actual crime. To address this question empirically, we would ideally experiment and introduce a source of random variation in the crime statistics. For instance, we could randomly increase or decrease the number of offences displayed in crime statistics and measure their effects on local house prices. For obvious reasons, we cannot pursue this research design. However, street-level crime maps contain intentional errors, which are the product of a geomasking algorithm designed to mask the location of crimes and protect the identity of victims. This project leverages features associated with the geomasking algorithm to estimate the effect of public crime statistics on house prices.

Fungal-Bacterial Networks in the Habitat of SongRong (Tricholoma matsutake) and Driving Factors of Their Distribution Rules.

Soil origin, mycorrhizal plant partners and environmental factors affect the growth and development of SongRong (Tricholoma matsutake). In order to clarify the relationships of fungi-bacteria networks and various influence factors in the habitat of SongRong, we chose three collection sites with a Quercus mongolica pure forest (plot A without SongRong was used as the control sample site), Q. mongolica mixed Rhododendron dauricum (plot B) and Q. mongolica mixed with R. dauricum and Pinus densiflora (plot C). By using high-throughput sequencing, we obtained a total of 4930 fungal and 55501 bacterial amplicon sequence variants (ASVs) based on internally transcribed spacer ribosomal RNA (ITS rRNA) and 16S ribosomal RNA (16S rRNA) sequencing via the Illumina NovaSeq platform. In the habitat soil of SongRong (plot B and plot C), alpha or beta diversity and species compositions of fungi and bacteria were different from plot A. The fungal-bacterial networks follow the selection rule that few dominant genera account for the greater relative abundance. Forest types, but not the host itself, drove the fungal-bacterial networks of the forest soil, and soil physicochemical characteristics and texture affected their abundance. The abundance of Tricholoma was affected by the fungal and bacterial abundance in the habitat.

Response of bacterial community structure to different ecological niches and their functions in Korean pine forests.

A healthy plant microbiome is diverse, taxonomically-structured, and gives its plant host moderate advantages in growth, development, stress tolerance, and disease resistance. The plant microbiome varies with ecological niches and is influenced by variables that are complex and difficult to separate from each other, such as the plant species, soil, and environmental factors. To explore the composition, diversity, and functions of the bacterial community of Korean pine forests, we used high-throughput sequencing to study five areas with different forest ages from June to October 2017 in northeast China. We obtained 3,247 operational taxonomic units (OTUs) based on 16S rRNA gene sequencing via an Illumina Hi-seq platform. A total of 36 phyla and 159 known genera were classified. The Shannon index of the bacterial community from the rhizospheric soil was significantly higher (p < 0.01, n = 10) than that of the root tips. Beta-diversity analysis confirmed that the bacterial community of the rhizospheric soil was significantly different (p < 0.001) from the root tips. Nine bacterial phyla were dominant (relative richness > 1%) in the rhizospheric soil, but there were six dominant phyla in the root tips. Proteobacteria was the core flora in the root tips with a relative abundance of more than 50%. It is known that the formation of bacterial communities in the rhizospheric soil or the root is mainly caused by the processes of selection, and we found a relatively high abundance of a few dominant species. We further analyzed the correlations between the bacterial community from the rhizospheric soil with that of the root tips, as well as the correlations of the bacterial community with soil physicochemical properties and climate factors. We used Functional Annotation of the Prokaryotic Tax (FAPROTAX) to predict the functions of the bacterial community in the rhizospheric soil and root tips. Five related phototrophic functions, nine nitrogen cycle functions, two related chemoheterotrophic functions, and two others were predicted. The abundance of the bacteria phyla performing relevant functions was different in the rhizospheric soil than in the root tips. These functions were significantly influenced by the contents of nitrogen, phosphorus, and potassium in the soil habitat. The bacterial composition and functions in the rhizospheric soil and root tips of Korean pine were analyzed, and the results demonstrated the importance of soil and plant species on the bacterial community in the below ground plant microbiome.

Morphological and Phylogenetic Evidence Reveal Five New Telamonioid Species of Cortinarius (Agaricales) from East Asia.

Five new Cortinarius species, C. neobalaustinus, C. pseudocamphoratus, C. subnymphatus, C. wuliangshanensis and C. yanjiensis spp. nov., are proposed based on a combination of morphological and molecular evidence. Cortinarius neobalaustinus is characterized by a very weakly hygrophanous and yellowish-brown to brown pileus and small and weakly verrucose basidiospores. Cortinarius pseudocamphoratus can be characterized by a viscid pileus, a strongly unpleasant smell, amygdaloid to somewhat ellipsoid basidiospores and lageniform to subfusiform cheilocystidia. Cortinarius subnymphatus is identified by a strongly hygrophanous pileus that is reddish-brown with a black-brown umbo, a yellowish universal veil and ellipsoid to subamygdaloid basidiospores. Cortinarius wuliangshanensis is characterized by a moderately to strongly hygrophanous, translucently striated and yellowish to reddish-brown pileus and rather weakly and moderately verrucose basidiospores. Cortinarius yanjiensis is distinguished by a weakly to moderately hygrophanous and yellowish to brown pileus and moderately to rather strongly verrucose basidiospores. The phylogenetic analyses were performed with maximum likelihood and Bayesian inference methods based on the data set of nuc rDNA ITS1-5.8S-ITS2 (ITS), D1-D2 domains of nuc 28S rDNA (28S) and RNA polymerase II second largest subunit (rpb2), and the results show that C. neobalaustinus, C. wulianghsanensis and C. yanjiensis cluster in sect. Illumini, C. pseudocamporatus belongs to sect. Camphorati and C. subnymphatus belongs to sect. Laeti. In addition, a study of basidiospores under field emission scanning electron microscopy (FESEM) was conducted. An identification key for the five new species and related species from China is also provided.

Cortinarius subsalor and C. tibeticisalor spp. nov., two new species from the section Delibuti from China.

Cortinarius subsalor and C. tibeticisalor, belonging to the section Delibuti, are described from China as new to science. Cortinarius subsalor has been found to be associated with Lithocarpus trees in subtropical China and resembling C. salor, but it differs from the later by having slender basidiomata and the narrower basidiospores. Cortinarius tibeticisalor was collected from eastern Tibetan Plateau, associated with Abies. It differs from other species within sect. Delibuti by having olive tinge of mature or dried basidiomata and bigger basidiospores. The molecular data also support C. subsalor and C. tibeticisalor as new species. The phylogenetic analyses and biogeography of sect. Delibuti are discussed and a key to the species of this section currently known in the world is provided.

Glycopeptidomics Analysis of a Cell Line Model Revealing Pathogenesis and Potential Marker Molecules for the Early Diagnosis of Gastric MALT Lymphoma.

Background & Aims: Gastric mucosa-associated lymphoma (GML) is a mature B cell tumor related to Helicobacter pylori (H.pylori) infection. The clinical manifestations of GML are not specific, so GML is often misdiagnosed, leading to excessive treatment. The pathogenesis of H.pylori-induced GML is not well understood and there are no molecular markers for early GML diagnosis. Methods: Glycopeptidomics analyses of host cell lines (a BCG823 cell line, C823) and C823 cells infected by H. pylori isolated from patients with GML (GMALT823), gastritis (GAT823), gastric ulcer (GAU823) and gastric cancer (GAC823) were carried out to clarify the host reaction mechanism against GML and to identify potential molecular criteria for the early diagnosis of GML. Results: Thirty-three samples were analyzed and approximately 2000 proteins, 200 glycoproteins and 500 glycopeptides were detected in each sample. O-glycans were the dominant glycoforms in GMALT823 cells only. Four specific glycoforms in GMALT823 cells and 2 specific glycoforms in C823 and GMALT823 cells were identified. Eight specific glycopeptides from 7 glycoproteins were found in GMALT823 cells; of these glycopeptides, 6 and 3 specific glycopeptides had high affinity for T cell epitopes and have conformational B cell epitopes, respectively. Conclusion: The predominant glycoforms of host cells infected by MALT H. pylori isolates differ from others, and the glycoproteins, glycosylation sites and glycoforms might be closely related to the formation of GML, which provides new insights into the pathogenic mechanisms of H. pylori infection and suggests molecular indicators for the early diagnosis of GML.

Palladium-Catalyzed Asymmetric (4 + 2) Annulation of γ-Methylidene-δ-valerolactones with Alkenes: Enantioselective Synthesis of Functionalized Chiral Cyclohexyl Spirooxindoles.

An unprecedented asymmetric catalytic (4 + 2) annulation reaction of aryl-substituted γ-methylidene-δ-valerolactones (GMDVs) with isatin-derived para-quinone methides (p-QMs) has been developed under the catalysis of palladium(0) and (S,S,S)-(-)-Xyl-SKP, offering a new approach for the diastereo- and enantioselective synthesis of chiral cyclohexadienone-fused cyclohexyl spirooxindoles. Significantly, three highly congested contiguous tetrasubstituted carbon atoms embedded in bispirocyclic skeleton, of which two are vicinal quaternary stereogenic centers, are forged in an effective and selective manner (up to 99% yield, up to 95% ee, >20/1 dr). The current reaction represents the first exploration of enantioselective catalytic (4 + 2) annulation forming the six-membered carbocycles in the chemistry of both GMDVs and p-QMs.

Social work contact in a UK cohort study: Under-reporting, predictors of contact and the emotional and behavioural problems of children.

BACKGROUND: There is little evidence on the degree of underreporting of social work contact in survey studies. There are also few studies about the emotional and behavioural problems of children in families who have contact with social workers, despite the adversities they face. OBJECTIVE: We examine underreporting of social work contact; the predictors of social work contact with families; and links between social work contact and emotional and behavioural outcomes for children. PARTICIPANTS AND SETTING: The Avon Longitudinal Study of Parents and Children follows the health and development of 14,062 children born in 1991-2 to women living in and around the City of Bristol. The study includes self-reported information about mothers' contact with social workers and children's emotional and behavioural outcomes using the Strengths and Difficulties Questionnaire (SDQ). METHODS: Self-reporting of social work contact in ALSPAC is compared with administrative data from the child protection register to examine rates of underreporting. We use a fixed-effects model to account for measurement error in estimating the association between social work contact and potential predictors, namely gender of the child and maternal factors: marital status, trouble with law, hospitalisation, cannabis and alcohol use, employment, financial difficulty and experience of cruelty from a partner. SDQ scores are explored using linear regression with lagged indicators of social work contact. RESULTS: The probability of a false negative for self-report of social work contact ranged from 22% to 34% across three survey waves. Mothers who married within the last 12 months were less likely to receive social work contact (OR: 0.13, CI95%: 0.01-1.34). Those who had either been hospitalised (OR: 1.52, CI95%: 1.01 - 2.28) or increased their rate of alcohol consumption (OR: 2.14, CI95%: 0.91 - 5.07) within the last 12 months were more likely to receive such contact. Overall children whose mothers report social work contact were much more likely to have emotional and behavioural problems within the first seven years of their lives (p < 0.01). CONCLUSION: There is potentially a high degree of underreporting of social work contact in social surveys and cohort studies. Researchers should adopt methods to account for this issue in the future. The risk of emotional and behavioural problems is greater among children whose mothers have had contact with social workers compared to other children with seemingly similar adversities.

Three new species of Cortinarius subgenus Telamonia (Cortinariaceae, Agaricales) from China.

Cortinarius is an important ectomycorrhizal genus that forms a symbiotic relationship with certain trees, shrubs and herbs. Recently, we began studying Cortinarius in China and here we describe three new species of Cortinarius subg. Telamonia based on morphological and ecological characteristics, together with phylogenetic analyses. Cortinarius laccariphyllus sp. nov. (section Colymbadini) is associated with broadleaf trees, with strongly hygrophanous basidiomata, special Laccaria-like lamellae and white and extremely sparse universal veil. Cortinarius neotorvus sp. nov. (section Telamonia) is associated with broadleaf trees and is easily confused with C. torvus, but can be distinguished by the colour of the fresh basidiomes and the stipe usually somewhat tapering towards the base. Cortinarius subfuscoperonatus sp. nov. (section Fuscoperonati) is associated with coniferous trees, with subglobose to broadly ellipsoid spores and is closely related to C. fuscoperonatus. A key to the new species and similar species in sections Colymbadini, Telamonia and Fuscoperonati is provided.

Electrocatalytic and Hg2+ Fluorescence Identifiable Bifunctional Sensors for a Series of Keggin Compounds.

By using a 2,2'-dimethyl-4,4'-bithiazole (dm4bt) ligand, Keggin polyanions, and different metal ions, nine Keggin-based compounds, namely, {[Ag(dm4bt)2][Ag2(dm4bt)3]}2(PW12O40)(H2PWV2WVI10O40) (1), [CuI(dm4bt)2][CuII(dm4bt)2(PW12O40)] (2), [CuI(dm4bt)2]4(SiW12O40) (3), {[Zn(dm4bt)2]2(SiW12O40)} (4), [Zn(dm4bt)2(H2O)]2(HPMoV2MoVI10O40)·2H2O (5), [Zn(dm4bt)2(Mo2O7)] (6), [Cd(dm4bt)3][Cd(dm4bt)2(H2O)(PMo12O40)]2·2H2O (7), [Cd(dm4bt)3](PMo12O40)·(Hdm4bt) (8), and [Cd(dm4bt)2(H2O)2]2(HPMoV2MoVI10O40)·2H2O (9), have been hydrothermally synthesized and characterized by single-crystal X-ray diffraction analysis, IR spectroscopy, and elemental analyses. Compounds 1-9 are zero-dimensional structures except compound 6, which exhibits a one-dimensional structure. In compound 1, there are three isolated subunits: Keggin anions, binuclear [Ag2(dm4bt)3]2+, and mononuclear [Ag(dm4bt)2]+ clusters. The binuclear [Ag2(dm4bt)3]2+ cluster has a Ag-Ag bond. In compound 2, a monosupporting anion {[CuII(dm4bt)2](PW12O40)}- and an isolated [Cu(dm4bt)2]+ cluster exist. By changing the transition metal ions, we obtained two different structures: a supramolecular 3 and a bisupporting anion in 4. By a one-pot method, we successfully obtained compounds 5 and 6, 7 and 8, respectively. In compound 5, the [Zn(dm4bt)2(H2O)]2+ subunit links adjacent PMo12 anions via S···O interactions to form a one-dimensional (1D) supramolecular chain. In compound 6, some PMo12 ions have transformed to [Mo2O7] n2 n- chains. The [Zn(dm4bt)2]2+ clusters buckle up and down the chain. Compound 7 has a monosupporting anion and an isolated [Cd(dm4bt)3]2+ cluster. Compound 8 has isolated anions and [Cd(dm4bt)3]2+ clusters. By changing the pH of 7 and 8, a distinct supramolecular compound 9 was obtained. Additionally, the optical band gap, electrochemical, and photocatalytic properties of 1-9 have been investigated in detail. The carbon paste electrodes can be used as bifunctional amperometric and fluorescence sensors for recognition of Hg2+. The n-CPEs as electrochemical sensors can show accurate selectivity for NO2- ions in some common ions. In the fluorescence sensor experiment, fluorescence intensities decrease more than 80% when quenched by Hg2+.

Hsp70-Bag3 complex is a hub for proteotoxicity-induced signaling that controls protein aggregation.

Protein abnormalities in cells are the cause of major pathologies, and a number of adaptive responses have evolved to relieve the toxicity of misfolded polypeptides. To trigger these responses, cells must detect the buildup of aberrant proteins which often associate with proteasome failure, but the sensing mechanism is poorly understood. Here we demonstrate that this mechanism involves the heat shock protein 70-Bcl-2-associated athanogene 3 (Hsp70-Bag3) complex, which upon proteasome suppression responds to the accumulation of defective ribosomal products, preferentially recognizing the stalled polypeptides. Components of the ribosome quality control system LTN1 and VCP and the ribosome-associated chaperone NAC are necessary for the interaction of these species with the Hsp70-Bag3 complex. This complex regulates important signaling pathways, including the Hippo pathway effectors LATS1/2 and the p38 and JNK stress kinases. Furthermore, under proteotoxic stress Hsp70-Bag3-LATS1/2 signaling regulates protein aggregation. We established that the regulated step was the emergence and growth of abnormal protein oligomers containing only a few molecules, indicating that aggregation is regulated at very early stages. The Hsp70-Bag3 complex therefore functions as an important signaling node that senses proteotoxicity and triggers multiple pathways that control cell physiology, including activation of protein aggregation.

Deep Sequencing of Complex Proteoglycans: A Novel Strategy for High Coverage and Site-specific Identification of Glycosaminoglycan-linked Peptides.

Proteoglycans are distributed in all animal tissues and play critical, multifaceted, physiological roles. Expressed in a spatially and temporally regulated manner, these molecules regulate interactions among growth factors and cell surface receptors and play key roles in basement membranes and other extracellular matrices. Because of the high degree of glycosylation by glycosaminoglycan (GAG), N-glycan and mucin-type O-glycan classes, the peptide sequence coverage of complex proteoglycans is revealed poorly by standard mass spectrometry-based proteomics methods. As a result, there is little information concerning how proteoglycan site specific glycosylation changes during normal and pathological processes. Here, we developed a workflow to improve sequence coverage and identification of glycosylated peptides in proteoglycans. We applied this workflow to the small leucine-rich proteoglycan decorin and three hyalectan proteoglycans: neurocan, brevican, and aggrecan.We characterized glycosylation of these proteoglycans using LC-MS methods easily implemented on instruments widely used in proteomics laboratories. For decorin, we assigned the linker-glycosite and three N-glycosylation sites. For neurocan and brevican, we identified densely glycosylated mucin-like regions in the extended domains. For aggrecan, we identified 50 linker-glycosites and mucin-type O-glycosites in the extended region and N-glycosites in the globular domains, many of which are novel and have not been observed previously. Most importantly, we demonstrate an LC-MS and bioinformatics approach that will enable routine analysis of proteoglycan glycosylation from biological samples to assess their role in pathophysiology.

Vitamin D receptor gene polymorphisms and the risk of multiple sclerosis: An updated meta-analysis.

BACKGROUND: The association between vitamin D receptor (VDR) gene polymorphisms and multiple sclerosis (MS) has been extensively studied, but results were controversial. METHODS: This meta-analysis aimed to confirm whether VDR gene polymorphisms were associated with MS. Meta-analysis on the association between MS and VDR ApaI, BsmI, TaqI and FokI polymorphisms were conducted using allelic contrast, recessive, homozygotes and dominant models. Data were extracted by standardized forms and odds ratios (OR) with 95% confidence intervals (CI) were calculated using the random effects model if the results were heterogeneous. Stratification analysis by the selected study characteristics were performed to detect potential source of heterogeneity. RESULTS: A total of 21 relevant studies involving 3593 MS patients and 3917 controls were included in the analysis. The association between TaqI polymorphism and MS risk was significant in the homozygous model (p = 0.006) indicated a significant protective effect of TT TaqI genotype. High latitude (40.1-50°N) was also found markedly influenced TaqI polymorphism and MS risk in the recessive and homozygous models (p = 0.045 and p = 0.015, respectively). Additionally, Asian or low latitude (20.1-30°N) people with ApaI homozygous genotype, '> 2013' publication year people in the allele contrast and dominant models of FokI, '> 40 years' age people with BsmI recessive model also indirectly significantly affected the association between VDR gene polymorphisms and MS risk. CONCLUSION: TaqI polymorphism is a significant protective factor for MS. However, the associations between ApaI, FokI and BsmI polymorphisms and MS were found only by study characteristics.

Variants in the Promoter Region of HLA-DQA1 were Associated with Idiopathic Membranous Nephropathy in a Chinese Han Population.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is an autoimmune disease and the leading cause of adult nephritic syndrome. HLA-DQA1 had been identified to be associated with IMN in Europeans and the result was replicated in Chinese Han population. In this study, six single nucleotide polymorphisms (SNPs) in the promoter of HLA-DQA1 and other two SNPs with IgA nephropathy were included for the association analysis. METHODS: The SNPs were genotyped in 509 patients and 601 controls by the MassArray iPLEX. The quantification of anti-phospholipase A2 receptor (PLA2R) antibodies in sera of IMN patients was performed by anti-PLA2R ELISA (IgG) kit. RESULTS: After analysis, four SNPs were significantly associated with IMN, with rs2187668 and rs28383345 as the top two signals (P = 8.42×10-5 and 2.48×10-5, respectively). Even under dominant model, the two SNPs were still significantly associated with IMN (P = 3.50×10-3 for rs28383345 and P = 6.55×10-5 for rs2187668). After conditional study with rs2187668, rs28383345 was the only variant significantly correlated with IMN after Bonferroni correction (P = 0.016). The minor alleles of the two SNPs were also mutually exclusive in our cohort. This indicated that the two SNPs were independently associated with IMN in Chinese Han population. Levels of anti-PLA2R autoantibodies were correlated with the genotypes of the two SNPs, but not significantly (P>0.05). CONCLUSIONS: Our results revealed that a novel independent variant in the promoter of HLA-DQA1 was associated with IMN in Chinese Han population. The locus possessed regulatory role according to the data of RegulomeDB. The exact role of the SNPs on the expression of HLA-DQA1 needs further investigation.