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1.
Clin Immunol ; 210: 108272, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683055

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multiple system involvement and positive serum autoantibodies. Lupus nephritis (LN) is the most common and serious complication of SLE, and it is the main cause of death in patients with SLE. Abnormalities in the immune system lead to LN and involve a variety of cells (T cells, B cells, macrophages, NK cells, etc.), cytokines (interleukin, tumor necrosis factor α, etc.) and their related pathways. Previous studies have shown that the interactions of genetic, epigenetic and environmental factors contribute to the pathogenesis and development of LN. In recent years, one genome-wide association study (GWAS) and a number of gene association studies have explored the susceptibility genes of LN, including immunization-, inflammation-, adhesion- and other pathway-related genes. These genes participate in or suggest the pathogenesis and progression of LN. In this review, we summarize the genetic susceptibility of LN and discuss the possible mechanism underlying the susceptibility genes of LN.

2.
Elife ; 82019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750832

RESUMO

Multiple subtypes of dopamine receptors within the GPCR superfamily regulate neurological processes through various downstream signaling pathways. A crucial question about the dopamine receptor family is what structural features determine the subtype-selectivity of potential drugs. Here, we report the 3.5-angstrom crystal structure of mouse dopamine receptor D4 (DRD4) complexed with a subtype-selective antagonist, L745870. Our structure reveals a secondary binding pocket extended from the orthosteric ligand-binding pocket to a DRD4-specific crevice located between transmembrane helices 2 and 3. Additional mutagenesis studies suggest that the antagonist L745870 prevents DRD4 activation by blocking the relative movement between transmembrane helices 2 and 3. These results expand our knowledge of the molecular basis for the physiological functions of DRD4 and assist new drug design.

3.
Clin Rheumatol ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31760539

RESUMO

In this study, we aimed to explore the expression levels of JAK2 and PTPRC in peripheral blood mononuclear cells (PBMCs) from SLE patients and controls, detect the effects of SLE activity on genes mRNA expression, and find the association between genes mRNA expression and clinical manifestations of patients. We performed quantitative real-time PCR (qRT-PCR) to test differences in the expression levels of JAK2 and PTPRC in PBMCs extracted from 135 patients with SLE and 130 healthy controls. Furthermore, we detected the regulatory effect of SNPs on gene expression by expression quantitative trait loci (eQTL). We also tested whether the genes mRNA expression was affected with the SLE activity and analyzed the relationship between genes mRNA expression and clinical manifestations of patients. The mRNA expression levels of JAK2 in SLE patients were significantly higher than those in healthy controls (P = 0.005), and PTPRC mRNA expression levels were significantly decreased (P < 0.001). However, no other statistical significance was detected. We found that the elevated JAK2 mRNA expression and the decreased PTPRC mRNA expression may play suggestive roles in the pathogenesis of SLE.Key Points• The JAK2 mRNA expression levels in SLE patients were significantly higher than those in healthy controls.• The PTPRC mRNA expression levels in SLE were decreased.• JAK2 and PTPRC mRNA expression may play suggestive roles in the pathogenesis of SLE.

4.
J Cosmet Dermatol ; 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31709745

RESUMO

BACKGROUND: Pretibial dystrophic epidermolysis bullosa (DEB-Pt) is an extremely rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by blistering and scar formation. The pathogenesis of the disease is mainly due to the mutation of COL7A1 gene encoding type VII collagen fibers, resulting in the destruction of the anchoring structure of the epidermis and dermis. AIMS: The purpose of this study was to discover the major mutations in DEB-Pt by studying this family and reviewing the literature on DEB-Pt. PATIENTS/METHODS: We examined the patients by clinical manifestations and histopathology, extracted DNA from blood samples from 7 individuals in the family via FlexiGene DNA Kit, and then sequenced the samples using whole-exon sequencing (WES). RESULT: Characteristic clinical manifestations such as blisters and scars were found in the patients. Genetic analysis revealed a missense mutation in exon 87(c.6860G>A) of COL7A1 gene, which has never been reported before. CONCLUSION: The discovery of the new mutation extends the COL7A1 mutation database. We also reviewed all the mutation in DEB-Pt from relevant literature at home and abroad. This will facilitate the molecular diagnosis, treatment, and prognosis of DEB-Pt.

5.
Epigenomics ; 11(14): 1613-1625, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31701765

RESUMO

Aim: To understand whether the anatomical location of origin plays a role in shaping the DNA methylation (DNAm) landscape of psoriatic skins. Patients & methods: A number of 108 psoriatic and 57 control skin samples were grouped based on their anatomical locations. Two group t-tests were used to identify those differentially methylated sites and regions. Target region methylation loci were validated by bisulfate conversion sequencing. The correlations of DNAm with pathological features, DNAm and gene expression were also interrogated. Results: Our analysis revealed 315 location-specific differentially methylated sites for back, 291 for the extremities and 801 for abdomen. Moreover, we observed that the extremity-specific loci cg21942490 located on HOXA9 is associated with hyperkeratosis. We further observed that HOXA5 and KIAA1949 are differential methylation regions. Conclusion: Our study shown evidence of anatomical location-dependent DNAm pattern in psoriasis skins, and thus provided new insights into the pathogenesis of this disease.

6.
Opt Express ; 27(21): 29803-29816, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684237

RESUMO

Traditional methods for distortion measurement of large-aperture optical systems are time-consuming and ineffective because they require each field of view to be individually measured using a high-precision rotating platform. In this study, a new method that uses a phase diffractive beam splitter (DBS) is proposed to measure the distortion of optical systems, which has great potential application for the large-aperture optical system. The proposed method has a very high degree of accuracy and is extremely economical. A high-precision calibration method is proposed to measure the angular distribution of the DBS. The uncertainty analysis of the factors involved in the measurement process has been performed to highlight the low level of errors in the measurement methodology. Results show that high-precision measurements of the focal length and distortion were successfully achieved with high efficiency. The proposed method can be used for large-aperture wide-angle optical systems such as those used for aerial mapping applications.

7.
PLoS One ; 14(11): e0225170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31730646

RESUMO

BACKGROUND: Serum des-γ-carboxy prothrombin (DCP) is a hepatocellular carcinoma (HCC) tumor marker that can be used to assess patient prognosis. Since the value of DCP in predicting the prognosis of hepatocellular carcinoma patients treated with transarterial chemotherapy remains controversial, we performed a meta-analysis of previous clinical studies. METHODS: A systematic literature search was performed using PubMed, the MEDLINE database, EMBASE, and the Cochrane Library in accordance with the PRISMA guidelines. The hazard ratio (HR) with 95% confidence interval (CI) was used to estimate the effect size. RESULTS: Six respective cohort studies including a total of 943 cases were identified. The pooled results showed that low DCP was associated with a favorable overall survival (OS)(HR 0.653, 95% CI 0.444-0.960), and DCP response was associated with increased OS (HR 0.387,95% CI 0.215-0.697) and progression-free survival (PFS) (HR 0.42,95% CI 0.23-0.74) in HCC patients treated with transarterial chemotherapy. CONCLUSIONS: DCP values in HCC patients undergoing hepatic arterial chemotherapy seem to be associated with OS and PFS. Thus, monitoring DCP values and observing the DCP response should be part of the management of patients undergoing transarterial chemotherapy.

8.
Arch Dermatol Res ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676945

RESUMO

Cutaneous T cell lymphoma (CTCL) is a rare but potentially devastating primary cutaneous lymphoma. CTCL is characterized by localization of neoplastic T lymphocytes to the skin, with mycosis fungoides (MF) and its leukemic form, Sézary syndrome (SS) being the most common variants. Thymocyte selection-associated high-mobility group box (TOX) gene has been found to be highly expressed in MF and SS. It is reported that higher expression levels of TOX in patients will increase risks of disease progression and poor prognosis. However, the molecular events leading to these abnormalities have not been well understood. To better understand the molecular mechanism underlying TOX-mediated differentially expressed genes (DEGs) in CTCL, and to identify DEGs pathways triggered after knockdown of TOX gene in the CTCL cell line Hut78, we employed two shRNA-mediated lentiviruses to knock down TOX gene in the skin lymphoma cell line HuT78. RNA sequencing (RNAseq) analysis was applied to analyze DEGs, DEGs GO and their corresponding pathways. Knockdown of TOX can induce upregulation of 547 genes and downregulation of 649 genes, respectively. HOXC9 was the most significant downregulated gene. Most DEGs are enriched in malignancies and relate to the Wnt and mTOR signaling pathways, and therefore they can regulate cellular processes and induce different biological regulation. Transcriptome analysis of DEGs after knockdown of TOX in our study provides insights into the mechanism of TOX in CTCL and suggests candidate targets for therapy of CTCL.

9.
Chin Med J (Engl) ; 132(20): 2417-2422, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31634243

RESUMO

BACKGROUND: Spider nevi (SN) are quite common in children. SN are treated via different techniques, and complete removal often requires multiple treatments. However, few studies have evaluated the treatment of SN. The present study aimed to evaluate the therapeutic effect and safety of a 595-nm pulsed-dye laser (PDL) for treating facial SN in children. METHODS: A total of 110 children aged 0.2 to 12 years with facial SN were treated with a 595-nm PDL in a single institution from January 2016 to February 2018. In accordance with the treatment method, the patients were retrospectively divided into the small-spot-combined-with-large-spot group (SL-group) and the large-spot group (L-group). Patients with poor therapeutic results were re-treated every 6 weeks until the lesions disappeared. The minimum follow-up period was 1 year. The groups were compared using independent-samples t tests, Mann-Whitney U test, Chi-square test, and Fisher exact probability test. RESULTS: The therapeutic efficacy was significantly higher in the SL-group than in the L-group, with clearance rates of 90.9% and 53.0% after the primary treatment, respectively (χ = 17.937, P < 0.001). For skin lesions with a central spider body diameter ≥1 mm, the once-treatment cure rates were 100% in the SL-group and 34.8% in the L-group (χ = 20.780, P < 0.001). For skin lesions with a central spider body diameter <1 mm, the once-treatment cure rates were 82.6% in the SL-group and 62.8% in the L-group (χ = 3.961, P = 0.138). The rates of adverse reactions and recurrence did not differ between the two groups (P = 0.141 and P = 1.000, respectively). CONCLUSIONS: The 595-nm PDL might be a safe and effective treatment option for facial SN in children. The small-spot-combined-with-large-spot method is especially suitable for SN with a central spider body diameter ≥1 mm.

10.
Pathol Res Pract ; 215(10): 152600, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31477326

RESUMO

Cutaneous squamous cell carcinoma (CSCC), a class of skin tumor derived from epidermal keratinocyte, is reputed as one of the most malignant tumors globally. MicroRNAs (miRNAs) are increasingly identified as essential players in CSCC. Current study aimed to uncover the impact and mechanism of miR-1193 in CSCC. We identified the low expression of miR-1193 in CSCC cell lines. Gain- and loss-of-function assays showed that miR-1193 acted as an inhibitor of proliferation and migration in CSCC cells. Furthermore, we illustrated that miR-1193 targeted and inhibited SRY-box 4 (SOX4), and that long intergenic non-protein coding RNA 963 (LINC00963) sponged miR-1193 to upregulate SOX4 expression. Rescue assays showed that LINC00963 regulated CSCC progression through miR-1193/SOX4 axis. In conclusion, our study firstly revealed the LINC00963/miR-1193/SOX4 axis in CSCC, indicating miR-1193 as a promising biological target in CSCC progression.

11.
Opt Lett ; 44(18): 4483-4486, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31517912

RESUMO

Surface plasmon resonance excitation with tilted fiber Bragg gratings has been typically studied using gold films to target biochemical sensing applications. However, surface plasmons can be excited on other metal coatings as well. In this work, plasmonic optical fiber grating platforms are developed using palladium films. Since the optical properties of this metal differ from the ones of gold, simulations are carried out to define the optimal thickness. Due to the phase transition of palladium in the presence of hydrogen, intensity changes in the optical transmission of the devices are produced. It is demonstrated that these platforms can be used for hydrogen detection at concentrations way below the lower explosive limit.

12.
J Rheumatol ; 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31523044

RESUMO

OBJECTIVE: We aimed to present a systematic evaluation of 47 non Major Histocompatibility Complex (MHC) Ankylosing Spondylitis (AS) susceptibility loci which have been initially discovered through Caucasian Genome-wide association studies (GWASs) in Han Chinese. METHODS: Totally 10,743 samples representing north and south Chinese in four datasets were obtained. After data quality control and imputation, meta-analysis results of 94,621 variants within 47 loci were extracted. Four ERAP1 single-nucleotide polymorphisms (SNPs) and HLA-B27 tag SNP rs13202464 were used for interaction analysis. Population-attributable risk percentages (PARPs) of AS-associated variants were compared. Functional annotation of AS-associated variants were conducted using HaploReg, RegulomeDB and rVarBase Database. RESULTS: We revealed 16 AS-associated variants with nominal evidence in Han Chinese, including rs10865331 (P=6.30×10-10), rs10050860 (P=4.09×10-5) and rs8070463 (P=1.03×10-4). Potential susceptible SNPs within these 47 loci were also identified, such as rs13024541 (2p15), rs17401719 (5q15) and rs62074054 (17q21). Epistatic ineractions between three ERAP1 SNPs (rs17401719, rs30187 and rs10050860) and HLA-B27 were confirmed. Among the 16 AS-associated variants, rs30187 showed weaker risk effect while rs10050860 and rs12504282 seemed to attribute more risk in Han Chinese than Caucasians. Further genomic annotation pinpointed 35 candidate functional SNPs, especially in 2p15, ERAP1 and NPEPPS-TBKBP1 region. CONCLUSION: Our results provided a detailed spectrum of all the reported non-MHC AS susceptibility loci in Han Chinese, which comprehensively exhibited the ethnic heterogeneity of AS susceptibility and highlighted that 2p15, ERAP1 and NPEPPS-TBKBP1 region may play a critical role in AS pathogenesis across diverse populations.

13.
J Invest Dermatol ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31376382

RESUMO

Most psoriasis-related genes or loci identified by genome-wide association studies (GWASs) represent common clusters and are located in noncoding regions of the human genome, providing only limited evidence for the roles of rare coding variants in psoriasis. Two exome-wide case-control genotyping data sets (11,245 cases and 11,177 controls) were obtained from our previous study. Quality controls were established for each data set, and the markers remaining in each set were annotated using ANNOVAR. Gene-based analysis was performed on the annotation results. A total of 250 and 35 genes in the Exome_Fine and Exome_Asian array cohorts, respectively, exceeded the threshold (P < 4.43 × 10-6). Merged gene-based analysis was then conducted on the same set of SNPs from seven genes common to both arrays, and the chi-square test was used to confirm all gene-based results. Ultimately, four susceptibility genes were identified: BBS7 (Pcombine = 1.38 × 10-29), GSTCD (Pcombine = 8.35 × 10-47), LIPK (Pcombine = 1.02 × 10-19) and PPP4R3B (Pcombine = 1.79 × 10-33). To our knowledge, this study identified four previously unreported susceptibility genes for psoriasis via a gene-based method using rare variants, contributing to our understanding of the pathogenesis of psoriasis.

14.
Cancer Immunol Res ; 7(11): 1803-1812, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31466995

RESUMO

Adoptive transfer of tumor-reactive T cells (ACT) has led to modest clinical benefit in the treatment of solid tumors. Failures with this therapy are primarily due to inadequate infiltration and poor function of adoptively transferred cells in the tumor microenvironment. To improve the efficacy of ACT, we combined ACT with dual blockade of CTLA-4 and PD-1. Treatment with anti-CTLA-4 plus anti-PD-1 compared with monotherapy resulted in durable antitumor responses, enhanced effector function of ACT, utilizing PMEL-1 transgenic (Tg+) CD8+ T cells, and improved survival. Using PMEL-1ICOS-/- mice, we showed that deletion of the inducible T-cell costimulator (ICOS) receptor abolished the therapeutic benefits, with selective downregulation of Eomesodermin (Eomes), interferon gamma (IFNγ), and perforin. Higher expression of IFNγ and Eomes was noted in human ICOShi CD8+ T cells compared with ICOSlow counterparts. Together, our data provide direct evidence that ACT combined with immune-checkpoint therapy confers durable antitumor responses, which largely depended on CD8+ T-cell-intrinsic expression of ICOS. Our study provides a foundation of testing combinatorial therapy of ACT of CD8 T cells and dual blocking of CTLA-4 and PD-1 in patients with melanoma.

15.
Biomaterials ; 218: 119328, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31299457

RESUMO

Bioavailable persistent luminescence material is an ideal internal light source for long-term photodynamic therapy, but inevitably suffers from low utilization efficiency and weak persistent luminescence due to corrosion and screening processes. Herein, we show a facile and smart "turning solid into gel" strategy to fabricate persistent luminescence hydrogel for high-efficient persistent luminescence-sensitized photodynamic therapy. The homogeneous persistent luminescence hydrogel was synthesized via dispersing high-temperature calcined persistent luminescence material without corrosion and screening into a biocompatible alginate-Ca2+ hydrogel. The simple synthesis strategy allows 100% of utilization efficiency and intact persistent luminescence of persistent luminescence material. The persistent luminescence hydrogel possesses favorable biocompatibility, bright persistent luminescence, red light renewability, good syringeability, and strong fixing ability in tumors. The persistent luminescence hydrogel can be easily injected in vivo as a powerful localized light source for superior persistent luminescence-sensitized photodynamic therapy of tumors. The "turning solid into gel" strategy enables taking full advantages of persistent luminescence for biological applications, and shows great potential in utilizing diverse theranostic agents regardless of hydrophilicity and hydrophobicity.

16.
Biophys J ; 116(12): 2296-2303, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31146923

RESUMO

Bacterial multidrug-resistance transporters of the major facilitator superfamily are distinguished by their extraordinary ability to bind structurally diverse substrates, thus serving as a highly efficient tool to protect cells from multiple toxic substances present in their environment, including antibiotic drugs. However, details of the dynamic conformational changes of the transport cycle involved remain to be elucidated. Here, we used the single-molecule fluorescence resonance energy transfer technique to investigate the conformational behavior of the Escherichia coli multidrug transporter MdfA under conditions of different substrates, pH, and alkali metal ions. Our data show that different substrates exhibit distinct effects on both the conformational distribution and transition rate between two major conformations. Although the cationic substrate tetraphenylphosphonium favors the outward-facing conformation, it has less effect on the transition rate. In contrast, binding of the electroneutral substrate chloramphenicol tends to stabilize the inward-facing conformation and decreases the transition rate. Therefore, our study supports the notion that the MdfA transporter uses distinct mechanisms to transport electroneutral and cationic substrates.

17.
Biochem Biophys Res Commun ; 513(2): 465-471, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-30967271

RESUMO

Cholangiocarcinoma (CCA) is the most usual malignancy of biliary tract, possessing a relatively low overall survival rate due to limited treatment options. Recently, long non-coding RNAs (lncRNAs) have been testified to have marked regulatory impacts on human cancers. The purpose of this paper is to explore the potent regulation mechanism of LINC01061 involved in CCA. Firstly, it was observed that LINC01061 expression was heightened in CCA cell lines, whose knockdown suppressed cell proliferation, induced cell apoptosis and restrained cell migration. Besides, LINC01061 existing in the cytoplasm of CCA cells interacted with miR-612. Moreover, subsequent experiments affirmed that LINC01061 regulated SEMA4D expression by acting as a competing endogenous RNA (ceRNA) of miR-612. At last, rescue assays validated that SEMA4D overexpression restored the repression caused by LINC01061 silence on the biological activities of CCA containing cell proliferation, apoptosis and migration. To sum up, our present exploration demonstrated that LINC01061 sponges miR-612 so as to upregulate SEMA4D expression for the progression of CCA, suggesting an optional promising and effective target for the therapy of patients with CCA.

18.
Ann Rheum Dis ; 78(6): 773-780, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30936065

RESUMO

OBJECTIVE: The strong genetic contribution of the major histocompatibility complex (MHC) region to rheumatoid arthritis (RA) has been generally attributed to human leukocyte antigen (HLA)-DRB1. However, due to the high polymorphisms and linkage disequilibrium within MHC, it is difficult to define novel and/or independent genetic risks using conventional HLA genotyping or chip-based microarray technology. This study aimed to identify novel RA risk variants by performing deep sequencing for MHC. METHODS: We first conducted target sequencing for the entire MHC region in 357 anticitrullinated protein antibodies (ACPA)-positive patients with RA and 1001 healthy controls, and then performed HLA typing in an independent case-control cohort consisting of 1415 samples for validation. All study subjects were Han Chinese. Genetic associations for RA susceptibility and severity were analysed. Comparative modelling was constructed to predict potential functions for the newly discovered RA association variants. RESULTS: HLA-DQα1:160D conferred the strongest and independent susceptibility to ACPA-positive RA (p=6.16×10-36, OR=2.29). DRß1:37N had an independent protective effect (p=5.81×10-16, OR=0.49). As predicted by comparative modelling, the negatively charged DQα1:160D stabilises the dimer of dimers, thus may lead to an increased T cell activation. The negatively charged DRß1:37N encoding alleles preferentially bind with epitope P9 arginine, thus may result in a decreased RA susceptibility. CONCLUSIONS: We provide the first evidence that HLA-DQα1:160D, instead of HLA-DRB1*0405, is the strongest and independent genetic risk for ACPA-positive RA in Han Chinese. Our study also illustrates the value of deep sequencing for fine-mapping disease risk variants in the MHC region.

19.
Arch Dermatol Res ; 311(4): 277-285, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30826962

RESUMO

To verify whether PsA-associated HLA alleles proposed in other populations are also related to PsA in Chinese Han population, a study of PsA susceptible alleles in the HLA-A, HLA-B, HLA-C and HLA-DRB1 alleles was presented for Chinese Han population. Genotyping was performed by Illumina Miseq platform (Illumina, USA). 50 subtypes and 77 subtypes of HLA-A, HLA-B, HLA-C and HLA-DRB1 with minor allele frequency (MAF) > 1% were genotyped from two-digit and four-digit resolution analysis in 111 PsA and 207 HCs (healthy controls) collected from Chinese Han population, respectively. Data handling, quality control and association analysis were performed using SPSS 25.0 software. In risk estimate, by mean of Bonferroni correction, a newfound four-digit allele HLA-A*01:01 [P = 5.5 × 10-4, OR 3.35 (1.69-6.66)], four-digit allele HLA-C*06:02 [P = 8.5 × 10-7, OR 3.80 (2.23-6.47)] and six two-digit alleles HLA-A*01 [P = 5.2 × 10-5, OR 3.43 (1.89-6.23)], HLA-B*13 [P = 4.0 × 10-6, OR 2.65 (1.76-4.01)], HLA-B*27 [P = 7.5 × 10-4, OR 5.84 (2.09-16.29)], HLA-B*57 [P = 5.8 × 10-5, OR 20.10 (4.65-86.83)], HLA-C*03 [P = 2.1 × 10-4, OR 0.40 (0.25-0.65)], HLA-C*06 [P = 1.9 × 10-12, OR 4.48 (2.95-6.81)] showed statistical significance by the univariate binary logistic regression analysis. Besides, in the binary logistic regression analysis with multiple variables, when the two alleles HLA-A*01:01 and HLA-C*06:02 were considered as covariates, HLA-A*01:01 [P = 2.7 × 10-3,OR 2.95 (1.46-5.98)] also showed significant association for PsA as risk factor, but may be not the main risk factor [HLA-C*06:02, P = 3.0 × 10-6, OR 3.68 (2.13-6.37)]. When all the above two-digit alleles were included as covariates, HLA-A*01 [P = 4.8 × 10-2, OR 2.00 (1.01-3.94)], HLA-B*13 [P = 4.2 × 10-5, OR 2.62 (1.65-4.16)], HLA-B*27 [P = 1.7 × 10-4, OR 7.62 (2.64-21.96)], HLA-B*57 [P = 2.97 × 10-4, OR 15.90 (3.55-71.18)], HLA-C*06 [P = 6.1 × 10-5, OR 2.70 (1.66-4.40)] showed significant for PsA as risk factors, HLA-C*03 [OR 0.65 (0.39-1.09), P = 0.10] showed no association with PsA. In conclusion, we assessed HLA-A, HLA-B, HLA-C and HLA-DRB1 alleles in PsA cohort of Chinese Han population, found HLA-A*01:01 and HLA-A*01 may be the susceptible genes associated with PsA, and also confirmed the association of four loci with PsA in Chinese Han population. These findings may extend the susceptibility HLA alleles of PsA and help in developing possible genetic markers to predict PsA.


Assuntos
Artrite Psoriásica/genética , Genótipo , Antígeno HLA-A1/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Estudos de Coortes , Feminino , Frequência do Gene , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Complexo Principal de Histocompatibilidade/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Risco , Adulto Jovem
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