Short-term exposure to gaseous pollutants is neglected factors for knee osteoarthritis: evidence from a humid subtropical region of China.

Few studies were performed on the impact of exposure to gaseous pollutants on the risk of knee osteoarthritis (KOA). We conducted this study to analyze the association between short-term exposure to gaseous pollutants and the risk of hospitalizations for KOA. A total of 2952 KOA hospitalizations derived from two hospitals in Hefei, and the relationship between gaseous pollutants and KOA hospitalizations was analyzed by a distributed lag non-linear model combined with a generalized linear model. We found that the decreased risk of hospitalizations for KOA were both related to exposure to NO2 (RR = 0.993, lag19 day) and O3 (RR = 0.984, lag0 day), while exposure to CO could increase the risk of hospitalizations for KOA (RR = 1.076, lag2 day). Stratified analyses suggested that the KOA patients < 65 years were more susceptible to O3 exposure, and the female, male, patients ≥ 65 years, and patients < 65 years were both more sensitive to CO exposure. Our findings demonstrated that exposure to NO2, O3 resulted in a decreased risk for KOA hospitalizations, and CO exposure might increase the risk of KOA hospitalizations.

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.

The Methylation in B7-H4 and BTLA Genes are Associated with the Risk of Pulmonary Tuberculosis.

Background: The important roles of B7 homologous body 4 (B7-H4), B and T lymphocyte attenuator (BTLA) in patients with pulmonary tuberculosis (PTB) have been reported. This study aims to evaluate the association among B7-H4 and BTLA genes polymorphism, methylation and PTB susceptibility. Methodology: Here, we assessed the possible relationship of 10 single nucleotide polymorphisms (SNPs) in B7-H4, BTLA genes with PTB susceptibility in a Chinese population (496 PTB patients and 502 controls) by SNPscan technique. Then, the B7-H4, BTLA genes methylation levels among 98 PTB patients and 97 controls were detected using MethylTarget technique. Results: This study found no significant differences in allele and genotype frequencies of B7-H4 gene rs10754339, rs10801935, rs10923223, rs1937956, rs3738414, BTLA gene rs1982809, rs2971205, rs75368388, rs9288953 variants between PTB patients and controls. Haplotype analysis suggested that the lower frequencies of B7-H4 AATTG haplotype, BTLA GATT haplotype and the higher frequency of BTLA AGTC haplotype were found in PTB patients when compared with controls. We also found that the frequency of BTLA gene rs9288953 C allele was significantly increased in PTB patients with drug resistance. Moreover, the methylation levels of B7-H4 and BTLA genes in PTB patients were greater than that in controls, and rs10754339 variant in B7-H4 gene could affect its methylation level in PTB patients. Conclusion: B7-H4, BTLA genes polymorphism might not affect PTB susceptibility, while the abnormal methylation levels of B7-H4, BTLA genes were associated with the genetic background of 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.

Clinical relevance of genetic polymorphisms in WNT signaling pathway (SFRP1, WNT3A, CTNNB1, WIF-1, DKK-1, LRP5, LRP6) on pulmonary tuberculosis in a Chinese population.

The present study was performed to evaluate the association of WNT signaling pathway genes variants with pulmonary tuberculosis (PTB) risk in Chinese Han population. Our study subjects were composed of 452 PTB patients and 465 normal controls, and seventeen SNPs of seven genes in WNT signaling pathway (SFRP1, WNT3A, CTNNB1, WIF-1, DKK-1, LRP5, LRP6) were genotyped by SNPscan technique. We found no significant relationship of SFRP1 rs10088390, rs4736958, rs3242, WNT3A rs752107, rs3121310, CTNNB1 rs2293303, rs1798802, rs4135385, WIF-1 rs1026024, rs3782499, DKK-1 rs2241529, rs1569198, LRP5 rs3736228, rs556442, LRP6 rs2302685, rs11054697, rs10743980 polymorphisms with PTB susceptibility. While, WIF-1 rs3782499 variant was associated with susceptibility to PTB under recessive model, and haplotype analysis showed that DKK-1 GA haplotype frequency was significantly increased in PTB patients. The WNT3A rs3121310, CTNNB1 rs2293303 polymorphisms were respectively associated with drug-induced liver injury (DILI), sputum smear-positive in PTB patients. The rs3782499 in WIF-1 gene was related to fever, leukopenia, and the rs1569198 in DKK-1 was linked to sputum smear-positive in PTB patients. In LRP5 gene, rs3736228, rs556442 variants respectively affected the occurrence of DILI, fever, and LRP6 gene rs2302685, rs10743980 variants respectively influenced the development of hypoproteinemia, sputum smear-positive in PTB patients. Our results revealed that WNT signaling pathway genes variation were not associated with the susceptibility to PTB, while WNT3A, CTNNB1, WIF-1, DKK-1, LRP5, LRP6 genetic variations might be closely related to the occurrence of several clinical characteristics of PTB patients.

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.

Exposure to ambient gaseous pollutant and daily hospitalizations for Sjögren's syndrome in Hefei: A time-series study.

Objective: Increasing evidence suggested that gaseous pollutants were associated with the development of autoimmune diseases, while there were few studies on the association between gaseous pollutants and Sjögren's syndrome (SS). This study sought to assess the relationship between exposure to several gaseous pollutants and the hospitalizations for SS. Methods: The data regarding SS hospitalizations, gaseous pollutants, and meteorological factors in Hefei from 2016 to 2021 were collected. A distributed lag non-linear model combined with a generalized linear model were adopted to analyze the association between gaseous pollutants and SS hospitalizations, and stratified analyses were also conducted. Results: We detected significant associations between gaseous pollutants (NO2, SO2, O3, CO) and SS hospitalizations. Exposure to NO2 was linked with the elevated risk of hospitalizations for SS (RR=1.026, lag1 day). A positive correlation between CO exposure and hospitalizations for SS was found (RR=1.144, lag2 day). In contrast, exposure to SO2, O3 was respectively related to the decreased risk of hospitalizations for SS (SO2: RR=0.897, lag14 day; O3: RR=0.992, lag9 day). Stratified analyses found that female patients were more vulnerable to these gaseous pollutants. SS patients ≥ 65 years were more susceptible to NO2, CO exposure, and younger patients were more vulnerable to O3 exposure. In addition, exposure to O3, CO in cold season were more likely to affect hospitalizations for SS. Conclusion: Our results demonstrated a significant association between exposure to NO2, CO and elevated risk of hospitalizations for SS, and SO2, O3 exposure might be linked to reduced risk of SS hospitalizations.

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.

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.

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.

Exposure to particulate pollutant increases the risk of hospitalizations for Sjögren's syndrome.

Objective: Numerous researches have reported the role of air pollution in the development of autoimmune diseases. However, few have evaluated the relationship between inhalable particulate matter (PM) exposure and Sjögren's syndrome (SS). This study aimed to analyze the association between exposure to two particulate pollutants (PM2.5, PM10) and SS-related hospitalizations. Methods: Daily data were obtained on PM2.5 and PM10, meteorological factors, and hospital hospitalizations for SS between 2016 and 2021. The daily data on PM2.5 and PM10, meteorological factors, and the number of SS hospitalizations were collected between 2016 and 2021. A distributed lag non-linear model and a generalized linear model were established to explore the association between PM2.5 and PM10 exposure and hospitalizations for SS. Stratified analyses were performed to explore possible gender-, age-, and season-related differences in PM2.5 and PM10 effects. Results: Exposure to PM2.5 was related to the evaluated risk of hospitalizations for SS (RR=1.015, 95% CI: 1.001-1.029, lag 3 day), similarly, PM10 exposure had a statistically significant positive association with SS hospitalizations (RR =1.013, 95% CI: 1.001-1.026, lag 3 day). Stratified analyses found that exposure to PM2.5 and PM10 exhibited higher impact on SS-related hospitalizations in female patients and exposure to PM2.5 was also associated with the higher risk of SS-related hospitalizations in patients aged ≥ 65 years. In addition, exposure to PM2.5, PM10 in colder season were more likely to increase SS-related hospitalizations. Conclusion: Our findings suggested that exposure to PM2.5 and PM10 were significantly linked to an elevated risk of hospitalizations for SS.

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.

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.

Association of NCF2, NCF4, and CYBA Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population.

OBJECTIVE: Recent studies have focused on the special roles of NADPH-oxidase in multiple autoimmune diseases. Nevertheless, the association of genetic variation in NADPH-oxidase genes with rheumatoid arthritis (RA) was not extensively studied in a Chinese population. We performed this study to examine the association of NCF2, NCF4, and CYBA gene polymorphisms with RA susceptibility in a Chinese population. METHODS: Six single nucleotide polymorphisms (SNPs) (NCF2 rs10911363, NCF4 rs1883112, rs4821544, rs729749, CYBA rs3794624, and rs4673) were genotyped in a cohort composed of 593 RA patients and 596 normal controls. Improved multiple ligase detection reaction (iMLDR) was used for genotyping. RESULTS: We observed that NCF4 rs4821544 CT genotype and C allele frequencies in RA patients were significantly decreased when compared to controls (CT vs. TT: P = 0.043; C vs. T: P = 0.031), and rs4821544 polymorphism was significantly associated with an increased RA risk under the dominant model (TT vs. CT+CC: P = 0.031). Our results also indicated that rs729749 CT genotype frequency was significantly lower in RA patients than that in controls (CT vs. CC: P = 0.033). Moreover, the rs729749 CT genotype frequency was also significantly decreased in RA patients in males (CT vs. CC: P = 0.024). No significant association between NCF2 and CYBA gene polymorphisms and RA susceptibility was observed. There were significant associations between rs4821544 TT genotype and T allele frequencies and anti-CCP in male RA patients. CONCLUSIONS: In summary, NCF4 rs4821544 and rs729749 polymorphisms might contribute to RA susceptibility, while NCF2 and CYBA gene polymorphisms were not associated with RA susceptibility.

Association of Leptin Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population.

BACKGROUND: Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. METHODS: We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. RESULTS: No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05). No significant difference in plasma leptin levels was detected between RA patients and controls (P > 0.05). CONCLUSION: Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.