Differences in the expression of long noncoding RNAs in peripheral blood mononuclear cells indicate potential biomarkers for rheumatoid arthritis.

OBJECTIVE: Long noncoding RNAs (lncRNAs) play an increasingly important role in various autoimmune diseases. We aimed to characterize the expression profiles of lncRNAs in peripheral blood mononuclear cells (PBMCs) from RA patients and to assess the potential of these lncRNAs as RA biomarkers. METHODS: Whole-transcriptome sequencing was used to establish a lncRNA expression profile. A total of 155 RA patients, 145 healthy controls, 59 systemic lupus erythematosus (SLE) patients and 59 primary Sjögren's syndrome (pSS) patients were recruited for this study. Four candidate lncRNAs (linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7) were validated via qRT-PCR in independent samples, and their expression, association with RA clinical features and value as RA biomarkers were evaluated. RESULTS: Linc00152 and lnc-ADM-1 exhibited upregulated expression (p = 0.001, p = 0.014, respectively), while ITSN1-2 and lnc-FTH1-7 exhibited downregulated expression (both p < 0.001, respectively) in RA patients compared to controls. Lnc-ADM-1 and lnc-FTH1-7 expression correlated positively with the C4 level (p = 0.016 and p = 0.012, respectively). ITSN1-2 levels were negatively associated with CRP levels (p = 0.024). Linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7 showed potential as RA biomarkers, with the four-lncRNA panel distinguishing RA patients from controls, SLE patients, or pSS patients (AUC = 0.886, 0.746, and 0.749, respectively). CONCLUSION: The altered expression of linc00152, lnc-ADM-1, ITSN1-2 and lnc-FTH1-7 in RA patients suggested that these genes may serve as potential biomarkers for RA and could be involved in its pathogenesis.

Association of lncRNA THRIL, HOTAIR genes variations and expression levels with pulmonary tuberculosis.

BACKGROUND: Long non-coding RNA (lncRNA) has been implicated in the pathogenesis of pulmonary tuberculosis (PTB). This study aims to investigate the involvement of lncRNA THRIL and HOTAIR gene single nucleotide polymorphisms (SNPs) and their expression levels in PTB susceptibility. METHODS: A total of 456 PTB patients and 464 healthy controls participated in our study. we genotyped six SNPs of THRIL and HOTAIR genes using an improved multiple ligase detection reaction (iMLDR). Additionally, real-time reverse-transcriptase polymerase chain reaction was employed to detect the expression levels of THRIL and HOTAIR in peripheral blood mononuclear cells (PBMC) from 78 PTB patients and 84 healthy controls. RESULTS: No significant differences in allele and genotype frequencies were observed for THRIL rs1055472, rs11058000, and HOTAIR rs12427129, rs1899663, rs4759314, and rs7958904 polymorphisms between PTB patients and healthy controls (all P > 0.05). Moreover, genotype frequencies of all SNPs did not show any association with PTB susceptibility in the dominant-recessive model. However, the frequencies of rs7958904 CC genotype and C allele in the HOTAIR gene were significantly correlated with leukopenia in PTB patients. Furthermore, the expression levels of the HOTAIR gene were significantly elevated in PTB patients compared to controls. CONCLUSIONS: Our study indicates that THRIL and HOTAIR gene SNPs might not contribute to PTB susceptibility, while the level of HOTAIR was increased in PTB patients.

A 1D/2D Bi2O3/g-C3N4 step-scheme photocatalyst to activate peroxymonosulfate for the removal of tetracycline hydrochloride: insight into the mechanism, reactive sites, degradation pathway and ecotoxicity.

A novel 1D/2D step-scheme Bi2O3/g-C3N4 was prepared using a simple reflux method. Bi2O3 photocatalysts showed lower photocatalytic activity for the degradation of tetracycline hydrochloride under visible light irradiation. After compositing with g-C3N4, the photocatalytic activity of Bi2O3 was enhanced obviously. The enhanced photocatalytic activity of the Bi2O3/g-C3N4 photocatalysts could be attributed to the high separation efficiency of carriers generated by the Bi2O3/g-C3N4 photocatalyst due to the formation of a step-scheme heterojunction, which inhibited the recombination of photogenerated electrons and holes. In order to further enhance the degradation efficiency of tetracycline hydrochloride, Bi2O3/g-C3N4 was used to activate peroxymonosulfate under visible-light irradiation. The influences of peroxymonosulfate dosage, pH value and tetracycline hydrochloride concentration on activating peroxymonosulfate to degrade tetracycline hydrochloride were investigated in detail. The mechanism of Bi2O3/g-C3N4 activating peroxymonosulfate was proved by radical quenching experiments and electron paramagnetic resonance analysis, which proved that the sulfate radical and hole dominated the degradation of tetracycline hydrochloride. The possible vulnerable sites and pathways of tetracycline hydrochloride were predicted via DFT calculations based on Fukui function and UPLC-MS. Toxicity Estimation Software predicts that the degradation processes of tetracycline hydrochloride could gradually reduce toxicity. This study could provide an efficient and green method for the subsequent treatment of antibiotic wastewater.

Roles of the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis.

Objective: The aim of the current study was to investigate the contributing role of gene variation and transcription levels among the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis (PTB). Methods: A case-control study including 461 PTB patients and 467 normal controls was designed for genotyping. Three SNPs in METTL3 (rs1061027, rs1139130, rs1061026), three SNPs in METTL14 (rs62328061, rs4834698, rs1064034), and two SNPs in WTAP (rs1853259, rs11752345) were genotyped via the SNPscan™ technique. METTL3, METTL14, and WTAP transcription levels were determined in 78 PTB patients and 86 controls via quantitative real-time reverse-transcription PCR. Results: Frequencies of the METTL14 rs62328061 GG genotype, WTAP rs11752345 CT genotype, and T allele were significantly increased in PTB patients compared to controls. An increased risk of rs62328061 was detected in a recessive model, and a decreased risk of rs11752345 was detected in a dominant model in the PTB group. METTL3 gene variation was not associated with PTB risk. The METTL3 rs1139130 GG genotype was significantly increased with drug resistance, and the G allele was significantly decreased with drug-induced liver injury in PTB patients. A reduced frequency of the METTL14 rs62328061 G allele was associated with leukopenia, a reduced frequency of the WTAP rs11752345 T allele was associated with sputum smear positivity, and a higher frequency of the METTL14 rs4834698 TC genotype was evident in PTB patients with hypoproteinemia. Compared to controls, METTL3, METTL14, and WTAP transcription levels in PTB patients were significantly decreased, and the level of WTAP was increased in PTB patients with drug resistance. METTL3 level was negatively associated with erythrocyte sedimentation rate and aspartate aminotransferase, and METTL14 level was negatively correlated with alanine aminotransferase and aspartate aminotransferase. Conclusion: METTL14 rs62328061 and WTAP rs11752345 variants were associated with the genetic background of PTB, and METTL3, METTL14, and WTAP levels were abnormally decreased, suggesting that these m6A methyltransferases may play important roles in PTB.

Exploring the association between Th17 pathway gene polymorphisms and pulmonary tuberculosis.

Th17 cells play a key role in immunity against Mycobacterium tuberculosis (MTB), and this study aimed to explore the association of Th17 pathway gene polymorphisms with pulmonary tuberculosis (PTB) susceptibility in a Chinese population. A total of 10 single nucleotide polymorphisms in Th17 pathway genes (IL-17A gene rs2275913, rs3748067, rs8193036, rs3819024, IL-17F gene rs7741835, rs763780, IL-21 gene rs907715, rs2055979, IL-23R gene rs11805303, and rs7518660) were genotyped in 456 PTB patients and 466 controls using SNPscan technique. The IL-23R rs11805303 CC genotype, C allele frequencies were significantly lower in PTB patients than in controls, and the rs11805303 variant was significantly associated with the reduced risk of PTB in a recessive model. There were no significant associations between IL-17A, IL-17F, and IL-21 gene variations and PTB risk. In IL-17A gene, rs2275913, rs3748067, and rs3819024 variants were associated with drug resistance in PTB patients. In IL-17F gene, rs7741835 variant affected drug resistance, and rs763780 variant was associated with hypoproteinemia in PTB patients. In addition, the lower frequencies of the TT genotype, T allele of rs2055979 were found in PTB patients with drug-induced liver injury. Haplotype analysis showed that IL-23R CG haplotype frequency was significantly lower in PTB patients than in controls, while the TG haplotype frequency was higher. In conclusion, IL-23R rs11805303 polymorphism may contribute to the genetic underpinnings of PTB in the Chinese population, and the IL-17A, IL-17F, and IL-21 genetic variations are associated with several clinical manifestations of PTB patients.

Synthesis of a ternary Bi2O3/CQDs/rGO photocatalyst to active peroxymonosulfate for the removal of tetracycline hydrochloride.

In this paper, the ternary Bi2O3/CQDs/rGO photocatalyst was synthesized by a solvothermal method. The as-fabricated Bi2O3/CQDs/rGO composites showed stronger visible-light response and higher photocatalytic activity. In order to further enhance the degradation efficiency of tetracycline hydrochloride, Bi2O3/CQDs/rGO was used to activate peroxymonosulfate under visible-light irradiation. The degradation efficiency increased sevenfold, indicating that the synergistic effect of photocatalysis and peroxymonosulfate activated by photogenerated electrons could clearly increase the degradation efficiency of tetracycline hydrochloride. In addition, the photocatalytic mechanism was further proposed and verified by radical quenching experiments and electron paramagnetic resonance analysis. Thus, this study provides a new idea for the photocatalytic application of Bi2O3/CQDs/rGO and a contribution to the degradation of antibiotics to avoid polluting the water environment.

Dickkopf-1 as a promising therapeutic target for autoimmune diseases.

Dickkopf-1 (DKK-1) is mostly known as a mature inhibitor of classic Wnt signaling pathways, which plays a critically role in regulating bone formation and bone metastasis. In recent years, the roles of DKK-1 played in bone resorption, bone formation, immune homeostasis and inflammation have been investigated. The role of DKK-1 in the pathogenesis and treatment of autoimmune diseases (ADs), including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), etc, has attracted widespread attention. Various studies have found that DKK-1 may be used as a biomarker for the occurrence and development of ADs, and as a potential target for the treatment of ADs. In this review, we have briefly summed up the intricate immunological functions and regulatory mechanisms of DKK-1 in ADs, aiming to further learning more about the role of DKK-1 involved in the pathogenesis of ADs and provide an outlook for the potential future researches.

Clinical relevance of vitamin B12 level and vitamin B12 metabolic gene variation in pulmonary tuberculosis.

The aim of this study was to assess the association of vitamin B12 level and single nucleotide polymorphisms (SNPs) in vitamin B12 metabolic genes with pulmonary tuberculosis (PTB) in Chinese Han population. The plasma vitamin B12 expression level was detected using ELISA. Ten SNPs in six key genes (TCN1, TCN2, CUBN, MMACHC, FUT6, and MUT) of vitamin B12 metabolic pathway were included for genotyping by the SNPscan technique among 454 PTB patients and 467 controls. Our results found that vitamin B12 level was significantly reduced in PTB patients when compared with controls. There was no significant association between TCN1 rs526934, TCN2 rs1801198, CUBN rs7906242, rs10904861, rs1801222, MMACHC rs10789465, FUT6 rs3760776, rs3760775, MUT rs9473555, rs9381784 variants, and PTB susceptibility. TCN2 rs1801198 CC genotype, C allele was significantly associated with hypoproteinemia in PTB patients. In CUBN, rs7906242 GG genotype, G allele, rs10904861 TT genotype, and T allele were significantly related to the decreased frequency of sputum smear-positive, and rs10904861 variant affected the occurrence of drug resistance in PTB patients. In addition, the increased frequency of CUBN rs1801222 AA genotype was significantly associated with leukopenia. The decreased frequency of MUT rs9473555 CC genotype was found in the PTB patients with hypoproteinemia. However, vitamin B12 expression was not associated with the genotype distribution of above SNPs. In conclusion, vitamin B12 level was significantly decreased in PTB patients and genetic variants in vitamin B12 metabolic genes were not contributed to PTB susceptibility. Several SNPs in TCN2, CUBN, and MUT gene might associate with multiple clinical manifestations in PTB.

Association of N6-methyladenosine readers' genes variation and expression level with pulmonary tuberculosis.

N6-Methyladenosine (m6A) is associated with many biological processes and the development of multiple diseases. The aim of this study was to analyze the association of m6A readers' genes variation, as well as their expression levels, with pulmonary tuberculosis (PTB). A total of 11 single-nucleotide polymorphisms (SNPs) in m6A readers' genes (i.e., YTHDF1 rs6122103, rs6011668, YTHDF2 rs602345, rs3738067, YTHDF3 rs7464, rs12549833, YTHDC1 rs3813832, rs17592288, rs2293596, and YTHDC2 rs6594732, and rs2416282) were genotyped by SNPscan™ technique in 457 patients with PTB and 466 normal controls. The m6A readers' genes expression levels in peripheral blood mononuclear cells (PBMCs) from 78 patients with PTB and 86 normal controls were detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). There was no significant association between all SNPs in YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 genes and PTB susceptibility. The increased frequencies of YTHDF2 rs3738067 GG genotype and YTHDC1 rs3813832 CC genotype, C allele, were, respectively, found in PTB patients with hypoproteinemia and fever. YTHDC2 rs6594732 variant was significantly associated with drug-induced liver damage and sputum smear-positive, and the rs2416282 variant was significantly associated with fever in patients with PTB. Compared with controls, the YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 mRNA levels were significantly decreased in PTB. Moreover, YTHDF1 level was negatively associated with erythrocyte sedimentation rate (ESR), and YTHDF3 and YTHDC1 levels were negatively related to alanine aminotransferase (ALT) in patients with PTB. Our results demonstrated that YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 genes SNPs did not contribute to PTB susceptibility, while their decreased levels in patients with PTB suggested that these m6A readers might play significant roles in PTB.

Synergetic effect of photocatalysis and peroxymonosulfate activated by MFe2O4 (M = Co, Mn, or Zn) for enhanced photocatalytic activity under visible light irradiation.

Nanosized MFe2O4 (M = Co, Mn, or Zn) photocatalysts were synthesized via a simple sol-gel method. MFe2O4 photocatalysts exhibited lower photocatalytic activity for the degradation of levofloxacin hydrochloride under visible light irradiation. For enhancement of photocatalytic activity, MFe2O4 was used to activate peroxymonosulfate and degrade levofloxacin hydrochloride under visible light irradiation. The influences of peroxymonosulfate dosage, levofloxacin hydrochloride concentration, pH value, and temperature on peroxymonosulfate activation to degrade levofloxacin hydrochloride were investigated in detail. The mechanism of activation of peroxymonosulfate by MFe2O4 was proposed and proved by radical quenching experiments, electron spin resonance analysis, X-ray photoelectron spectroscopy, electrochemical impedance spectroscopy, and transient photocurrent responses. The combined activation effects of photogenerated e-/h+ and transition metals on peroxymonosulfate to produce sulfate radical clearly enhanced the degradation efficiency.

Investigation on Probable Association Between IL-13, IL-13RA1, and IL-13RA2 Genes Polymorphism and Pulmonary Tuberculosis.

Objective: Our study aimed to explore the association of IL-13, IL-13RA1, and IL-13RA2 genes polymorphisms with PTB susceptibility and its clinical features. Methods: Nine SNPs were genotyped by improved multiple ligase detection reaction (iMLDR) in 476 PTB patients and 473 controls. The association between these SNPs and PTB risk was analyzed using SPSS software and haplotype analysis was assessed using SHEsis software. Results: The IL-13RA1 rs2495636 GA genotype frequency in PTB patients was significantly decreased, and IL-13RA2 rs5946039 A allele was related to the lower risk of PTB. In IL-13 gene, rs20541 variant was found to be associated with PTB risk under recessive mode. Moreover, IL-13RA1 rs141573089 C allele was significantly lower in PTB presenting with fever, drug resistance, and CC genotype was decreased in PTB presenting with leukopenia. IL-13RA1 rs2495636 polymorphism was associated with drug resistance, pulmonary infection, and IL-13RA2 rs3795175, rs638376 polymorphisms were related to drug resistance in PTB patients. Conclusion: IL-13 rs20541, IL-13RA1 rs2495636, IL-13RA2 rs5946039 polymorphisms might be contributed to the genetic background of PTB in Chinese population.

Association Between Genetic Polymorphisms of lncRNA NEAT1 and Pulmonary Tuberculosis Risk, Clinical Manifestations in a Chinese Population.

Background: Recent studies have shown that abnormal expression of lncRNA NEAT1 is associated with the progression of pulmonary tuberculosis (PTB). The aim of our study was to analyze the relationship between single nucleotide polymorphisms (SNPs) of NEAT1 gene and susceptibility to PTB. Methods: Four SNPs (rs2239895, rs3741384, rs3825071, rs512715) in NEAT1 gene were genotyped in 479 patients with PTB and 476 controls by improved multiple ligase detection reaction (iMLDR) in a Chinese population. Results: We found no significant differences in allele and genotype frequencies of NEAT1 gene rs2239895, rs3741384, rs3825071, rs512715 between PTB patients and controls (all P > 0.05). There was no statistically significant association between genotype frequency distribution of dominant model, as well as recessive model, and genetic susceptibility to PTB patients (all P > 0.05). The TT genotype, T allele frequencies of rs3825071 were significantly increased in sputum smear-positive PTB patients when compared to sputum smear-negative PTB patients (P = 0.010, P = 0.003, respectively). Haplotype analysis shown that NEAT1 haplotype frequency was not associated with PTB susceptibility. Conclusion: NEAT1 gene polymorphisms were not associated with the risk of PTB in Chinese population, and rs3825071 polymorphism might be related to sputum smear-positive in PTB patients.

The Contribution of Genetic Variation and Aberrant Methylation of Aryl Hydrocarbon Receptor Signaling Pathway Genes to Rheumatoid Arthritis.

The aryl hydrocarbon receptor (AHR) signaling pathway participates in immune regulation of multiple autoimmune diseases, including rheumatoid arthritis (RA). We conducted this study to investigate the association of AHR signaling pathway genes (AHR, ARNT, AHRR) single nucleotide polymorphisms (SNPs), as well as their methylation levels, with RA susceptibility. Nine SNPs (AHR gene rs2066853, rs2158041, rs2282885, ARNT gene rs10847, rs1889740, rs11204735, AHRR gene rs2292596, rs2672725, rs349583) were genotyped via improved multiple ligase detection reaction (iMLDR) in 479 RA patients and 496 healthy controls. We used the Illumina Hiseq platform to detect methylation levels of these genes in 122 RA patients and 123 healthy controls. A significant increase in rs11204735 C allele frequency was observed in RA patients when compared to controls. Further, rs11204735 polymorphism was associated with a decreased risk of RA under the dominant model. ARNT CCC haplotype frequency was significantly increased in RA patients in comparison to controls. In the AHRR gene, rs2672725 GG genotype, G allele frequencies were significantly related to an increased risk of RA and rs2292596, rs2672725 polymorphism were significantly associated with an increased risk of RA under the dominant model, recessive model, respectively. However, no significant association was identified between AHR gene polymorphism and RA susceptibility. The AHR methylation level in RA patients was significantly higher than the controls, while AHRR methylation level was abnormally reduced in RA patients. In addition, AHRR rs2672725 genotype distribution was significantly associated with the AHRR methylation level among RA patients. In summary, ARNT rs11204735, AHRR rs2292596, and rs2672725 polymorphisms were associated with RA susceptibility and altered AHR, AHRR methylation levels were related to the risk of RA.

Association of leptin and leptin receptor genes variants and pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population.

BACKGROUND: The aim of our study was to investigate the association of leptin (LEP) gene (rs11761556, rs12706832, rs2167270), leptin receptor (LEPR) gene (rs1137100, rs1137101, rs1805096) variants and pulmonary tuberculosis (PTB) susceptibility, as well as their several clinical manifestations, in a Chinese population. METHODS: This study included a cohort of 489 PTB patients and 489 healthy controls, and six SNPs were genotyped by improved multiple ligase detection reaction (iMLDR). RESULTS: We found that there were no significant differences regarding the allele and genotype frequencies of LEP rs11761556, rs12706832, rs2167270, LEPR rs1137100, rs1137101, rs1805096 between PTB patients and healthy controls (all P > 0.05), as well as the results of the dominant model and recessive model (all P > 0.05). In the LEP gene, the rs11761556 AA genotype frequency was significantly associated with the development of fever and pulmonary infection in PTB patients (P = 0.035, P = 0.049). In addition, the relation between main haplotypes and PTB patients was also analyzed, but only haplotype CAG in LEP was significantly associated with PTB susceptibility (P = 0.012). CONCLUSIONS: LEP and LEPR heritable variation were not contribute to the pathogenesis of PTB in Chinese. While rs11761556 variant might associate with several clinical features of PTB.

No Genetic Causal Association Between Periodontitis and Arthritis: A Bidirectional Two-Sample Mendelian Randomization Analysis.

Objectives: Periodontitis (PD) has been linked to arthritis in previous epidemiological observational studies; however, the results are inconclusive. It remains unclear whether the association between PD and arthritis is causal. The purpose of this study was to investigate the causal association of PD with arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA). Methods: We performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy. Results: Genetically determined PD did not have a causal effect on OA (OR = 1.06, 95% CI: 0.99-1.15, P = 0.09) and RA (OR = 0.99, 95% CI: 0.87-1.13, P = 0.89). Furthermore, we did not find a significant causal effect of arthritis on PD in the reverse MR analysis. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates according to the sensitivity analysis. Conclusions: Our MR analysis reveals non-causal association of PD with arthritis, despite observational studies reporting an association between PD and arthritis.

Impact of m6A demethylase (ALKBH5, FTO) genetic polymorphism and expression levels on the development of pulmonary tuberculosis.

Objective: The m6A methylation was involved in the pathogenesis of pulmonary tuberculosis (PTB), and our study aimed to reveal the potential association of m6A demethylase (ALKBH5, FTO) genes variation, expression levels and PTB. Methods: Eight SNPs (ALKBH5 gene rs8400, rs9913266, rs12936694, rs4925144 and FTO gene rs6499640, rs8047395, rs1121980, rs9939609) were selected for genotyping by SNPscan technique in 449 PTB patients and 463 healthy controls. Results: The mRNA expression levels of ALKBH5, FTO were detected by qRT-PCR. There were no significant differences in genotype, allele distributions of all SNPs between PTB patients and healthy controls. Haplotype analysis demonstrated that the frequency of FTO gene GAAA haplotype was significantly reduced in PTB patients when compared to controls. ALKBH5 rs8400 AA genotype, A allele frequencies were associated with the decreased risk of sputum smear-positive, while AA genotype frequency was related to the increased risk of hypoproteinemia in PTB patients. In addition, rs9913266 variant was linked to the occurrence of drug-induced liver injury, sputum smear-positive, and rs4925144 variant was associated with leukopenia among PTB patients. In FTO gene, rs8047395 GG genotype and G allele frequencies were significantly higher in the PTB patients with drug resistance than that in the PTB patients without drug resistance. The ALKBH5, FTO expression levels were significantly decreased in PTB patients in comparison to controls. Moreover, ALKBH5 level was increased in PTB patients with drug resistance, and FTO level was decreased in PTB patients with sputum smear-positive. Conclusion: FTO gene polymorphisms might be associated with PTB susceptibility, and ALKBH5, FTO levels were decreased in PTB patients, suggesting that these m6A demethylase played important roles in PTB.

Vitamin D Metabolic Pathway Genes Polymorphisms and Their Methylation Levels in Association With Rheumatoid Arthritis.

Abnormal vitamin D metabolism is involved in the pathogenesis of rheumatoid arthritis (RA). In this study, we evaluated the association of single nucleotide polymorphisms (SNPs) and methylation levels in vitamin D metabolic pathway genes with RA susceptibility. Ten SNPs in vitamin D metabolic pathway genes (CYP2R1, CYP24A1, VDR, CYP27B1) were genotyped in 477 RA patients and 496 controls by improved multiple ligase detection reaction (iMLDR). The methylation levels of the promoter regions of these genes were detected in 122 RA patients and 123 controls using Illumina Hiseq platform. We found that the CYP2R1 rs1993116 GA genotype, CYP27B1 rs4646536 GA genotype, rs4646536 A allele frequencies were significantly increased in RA patients when compared to controls. The decreased risk of rs1993116, rs4646536 was found under the dominant mode in RA patients. However, no significant association was found between CYP2R1 rs7936142, rs12794714, CYP24A1 rs2762934, rs6068816, rs2296239, rs2296241, VDR rs11574129, rs3847987 polymorphism, and RA susceptibility. The VDR, CYP27B1 methylation levels in RA patients were significantly lower than those in controls, while CYP2R1, CYP24A1 methylation levels were not associated with RA. There were no statistical associations between CYP2R1, CYP24A1, VDR, CYP27B1 methylation levels and their respective genotype in RA patients. In addition, plasma 25OHD level in RA patients was significantly lower than that in healthy controls. In summary, our results showed that CYP2R1, CYP27B1 genetic variations were associated with the genetic background of RA, while altered VDR, CYP27B1 methylation levels were related to the risk of RA.

Altered NCF2, NOX2 mRNA Expression Levels in Peripheral Blood Mononuclear Cells of Pulmonary Tuberculosis Patients.

BACKGROUND: Reactive oxygen species (ROS) generated by NADPH oxidase has a pivotal role in the nonspecific innate immune response to invading microorganisms including M. tuberculosis (MTB). NCF2 and NOX2 were considered as important functional subunits of NADPH oxidase complex; hence, this study aimed to evaluate the NCF2, NOX2 mRNA expressions in PBMC of pulmonary tuberculosis (PTB) patients. METHODS: A total of 79 PTB patients and 73 controls were included in our study. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to measure the NCF2, NOX2 mRNA levels, and receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic value of NCF2, NOX2 in PTB patients. RESULTS: When compared to controls, the NCF2, NOX2 mRNA levels were significantly increased in PBMC from PTB patients (P < 0.001). However, the NCF2, NOX2 mRNA levels were not associated with major clinical and laboratory data of PTB patients. Area under curve (AUC) of ROC curve analysis for NCF2 and NOX2 were 0.686 (95% CI: 0.601, 0.770) and 0.705 (95% CI: 0.623, 0.787), respectively. CONCLUSION: Altered NCF2, NOX2 mRNA levels in PTB patients implied that these genes might play roles in PTB, and their expression levels might be potential biomarkers for the diagnosis of PTB.

Application of Copy Number Variation Detection to Fetal Diagnosis of Echogenic Intracardiac Focus During Pregnancy.

Echogenic intracardiac focus (EIF) is one of the most common ultrasound soft markers (USMs) in prenatal screening. However, the association of EIF with chromosomal abnormalities is still controversial. From January 2018 to April 2020, a total of 571 fetuses with USMs in our center were enrolled, among which 150 (26.27%) presented EIFs. We analyzed the karyotype anomalies and copy number variations (CNVs) in fetuses who presented EIFs by comparing their ultrasound indications, maternal ages and gestational stages. There were no statistically significant differences in the incidence of chromosomal abnormalities between fetuses with EIFs and the fetuses with USMs (4.00 vs. 7.71%, p = 0.112). Additionally, the incidence of chromosomal abnormalities was not related to maternal age (4.10% in maternal age below 35 yeas vs. 3.57% in maternal age above 35, p = 1.000). Interestingly, after 28 weeks of gestation, fetuses with EIFs showed more chromosomal abnormalities (20.00%) than that in the group before 28 weeks of gestation (2.22%, p = 0.014), and this result was attributed to the detection of pathogenic CNVs. After birth, 25 of children conducted cardiac development re-examination. Among them, 9 (36%, 9/25) were diagnosed with congenital heart disease, primarily patent foramen oval and ventricular septal defects (7/9, 77.77%). We concluded that the appearance of EIFs in early or mid-trimester would not indicate an increased risk of fetal chromosomal abnormalities. However, the persistence of EIFs in late trimester was associated with a higher risk of pathology-related CNVs and its persistent appearance may indicate heart development defects after birth. Thus, our results suggest that CNV detection has its advantages in prenatal diagnosis, especially for those with EIFs that persist in the third trimester.

Association of vitamin D pathway genes polymorphisms with pulmonary tuberculosis susceptibility in a Chinese population.

OBJECTIVE: This study aimed to evaluate the association of single nucleotide polymorphisms (SNPs) of vitamin D metabolic pathway genes with susceptibility to pulmonary tuberculosis (PTB). METHODS: Nine hundred seventy-nine patients (490 PTB cases and 489 healthy controls) were included in this study. Seventeen SNPs of vitamin D metabolic pathway genes, including CYP24A1, CYP27A1, CYP27B1, CYP2R1, GC, and DHCR7, were genotyped with improved multiple ligase detection reaction (iMLDR). RESULTS: The GC rs3733359 GA, rs16847024 CT genotypes were significantly associated with the reduced risk of PTB, and the rs3733359 A, rs16847024 T alleles were also associated with the decreased PTB susceptibility. The GT genotype of GC rs4588 variant was significantly higher in patients with PTB when compared to controls. Moreover, the increased risk of rs3733359 and rs16847024 variants, and a decreased risk of rs4588, were found under the dominant mode among the PTB patients. However, there was no significant relationship of CYP24A1, CYP27A1, CYP27B1, CYP2R1, and DHCR7 polymorphisms with the risk of PTB. In CYP27A1, the rs17470271 T and rs933994 T alleles were significantly associated with leukopenia, drug resistance in the PTB patients, respectively. In GC gene, the rs7041 and rs3733359 variants were found to be associated with pulmonary infection, fever in the PTB patients, respectively. The increased frequency of rs16847024 TT genotype was found in the PTB patients with fever and drug-induced liver damage. DHCR7 rs12785878 TT genotype, and T allele frequencies were both significantly associated with pulmonary infection in the PTB patients. The haplotype analysis showed that CYP24A1 TACT, CYP2R1 GGCT, GGAT, GC AATG haplotypes were related to PTB susceptibility. CONCLUSION: Our study suggested that GC SNPs were associated with the genetic background of PTB. CYP27A1, GC, and DHCR7 genetic variations might contribute to several clinical phenotypes of PTB in Chinese.