Association of LncRNA-GAS5 gene polymorphisms and PBMC LncRNA-GAS5 level with risk of systemic lupus erythematosus in Chinese population.

Growth arrest-specific 5 (GAS5) is a kind of long non-coding RNAs (lncRNAs). Previous studies showed that down-regulation of LncRNA-GAS5 was involved in the development of systemic lupus erythematosus (SLE). However, the regulatory mechanism of down-expressed LncRNA-GAS5 in SLE remains obscure. In this study, we aimed to investigate the association of LncRNA-GAS5 polymorphism with SLE risk. And further explore how LncRNA-GAS5 is involved in the occurrence of SLE. Here, we evaluated the relationship between the risk for the development of SLE and the 5-base pair (AGGCA/-) insertion/deletion (I/D) polymorphism (rs145204276) in the LncRNA-GAS5 promoter region. A custom 36-Plex SNPscan kit was used for genotyping the LncRNA-GAS5 polymorphisms. The LncRNA-GAS5 and miR-21 target prediction was performed using bioinformatics software. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR) were performed to assess GAS5 and miR-21 mRNA expression and PTEN protein expression. The results revealed that rs145204276 resulted in a decreased risk of SLE (DD genotypes vs II genotypes: adjusted OR = 0.538, 95% CI, 0.30-0.97, P = .039; ID genotypes vs II genotypes: adjusted OR = 0.641, 95% CI, 0.46-0.89, P = .007; ID/DD genotypes vs II genotypes: adjusted OR = 0.621, 95% CI, 0.46-0.84, P = .002; D alleles vs I alleles: adjusted OR = 0.680, 95% CI, 0.53-0.87, P = .002). A reduced incidence of renal disorders in SLE was found to be related to ID/DD genotypes and D alleles (ID/DD genotypes vs II genotypes: OR = 0.57, 95% CI, 0.36-0.92, P = .020; D alleles vs I alleles: OR = 0.63, 95% CI, 0.43-0.93, P = .019). However, no significant association of rs2235095, rs6790, rs2067079 and rs1951625 polymorphisms with SLE risk was observed (P > .05). Additionally, haplotype analysis showed that a decreased SLE risk resulted from the A-A-C-G-D haplotype (OR = 0.67, 95% CI, 0.49-0.91, P = .010). Also, patients in the SLE group showed a down-regulated expression of LncRNA-GAS5 and PTEN than the healthy volunteers; however, patients with rs145204276 ID/DD genotypes showed up-regulated expression of LncRNA-GAS5 and PTEN compared with patients carrying the II genotype. Furthermore, the miR-21 levels were considerably up-regulated in the SLE group than the healthy volunteers, and patients with rs145204276 ID/DD genotype had lower miR-21 levels than the ones with the II genotype. Thus, we found that the LncRNA-GAS5/miR-21/PTEN signalling pathway was involved in the development of SLE, where LncRNA-GAS5 acted as an miR-21 target, and miR-21 regulated the expression of PTEN. These findings indicated that the rs145204276 ID/DD genotypes in the LncRNA-GAS5 gene promoter region may be protected against SLE by up-regulating the expression of LncRNA-GAS5, which consecutively regulated miR-21 and PTEN levels.

A genetic variant in the promoter of lncRNA MALAT1 is related to susceptibility of ischemic stroke.

BACKGROUND: Metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) was aberrantly expressed in diverse diseases. Particularly in ischemic stroke (IS), the abnormal expression of MALAT1 played important roles including promotion of angiogenesis, inhibition of apoptosis and inflammation and regulation of autophagy. However, the effects of genetic variation (single nucleotide polymorphisms, SNPs) of MALAT1 on IS have rarely been explored. This study aimed to investigate whether SNPs in promoter of MALAT1 were associated with the susceptibility to IS. METHODS: A total of 316 IS patients and 320 age-, gender-, and ethnicity-matched controls were enrolled in this study. Four polymorphisms in the promoter of MALAT1 (i.e., rs600231, rs1194338, rs4102217, and rs591291) were genotyped by using a custom-by-design 48-Plex SNPscan kit. RESULTS: The rs1194338 C > A variant in the promoter of MALAT1 was associated with the risk of IS (AC vs. CC: adjusted OR = 0.623, 95% CI, 0.417-0.932, P = 0.021; AA vs. CC: adjusted OR = 0.474, 95% CI, 0.226-0.991, P = 0.047; Dominant model: adjusted OR = 0.596, 95% CI, 0.406-0.874, P = 0.008; A vs. C adjusted OR = 0.658, 95% CI, 0.487-0.890, P = 0.007). The haplotype analysis showed that rs600231-rs1194338-rs4102217-rs591291 (A-C-G-C) had a 1.3-fold increased risk of IS (95% CI, 1.029-1.644, P = 0.027). Logistic regression analysis identified some independent impact factors for IS including rs1194338 AC/AA, TC, TG, HDL-C, LDL-C, Apo-A1, Apo-B and NEFA (P < 0.05). CONCLUSIONS: These results suggest that the rs1194338 AC/AA genotypes may be a protective factor for IS.

A functional polymorphism in the promoter of TUG1 is associated with an increased risk of ischaemic stroke.

Taurine-upregulated gene 1 (TUG1), a kind of long non-coding RNAs (lncRNAs), was up-regulated in ischaemic stroke (IS) with the function of promoting neuron apoptosis. In this study, we aimed to investigate the association of TUG1 polymorphisms with IS risk. The TUG1 polymorphisms were genotyped using a custom-by-design 48-Plex SNPscan kit. The promoter activity was measured using the dual luciferase reporter assay. Relative expression of TUG1 in IS patients was analysed using quantitative PCR and the binding of TUG1 rs2240183 polymorphism to transcription factor was analysed using chromatin immunoprecipitation (ChIP) assay. The rs2240183 CT/CC genotypes and C allele in the promoter of TUG1 were associated with an increased risk of IS (CT/CC vs. TT: adjusted OR = 1.70, 95% CI, 1.16-2.49, P = 0.006; C vs. T: adjusted OR = 1.47, 95% CI, 1.12-1.93, P = 0.005). Logistic regression analysis showed that the rs2240183 was a risk factor of IS besides TC, TG, HDL-C, LDL-C, VLDL-C, Apo-A1, Apo-B and NEFA. Further functional analysis revealed that the TUG1 rs2240183 C allele exhibited higher transcriptional activity and TUG1 expression levels (P < 0.01). The ChIP assay showed that the rs2240183 C allele binds to transcriptional factor GATA-1. These findings indicate that the rs2240183 C allele was associated with a higher risk of IS possibly by binding to GATA-1 and elevating TUG1 levels.

A functional variant rs12904 in the miR-200c binding site was associated with a decreased risk of ischemic stroke.

Genome-wide association study (GWAS) identified chromosome 12p13 rs12425791 and rs11833579 as susceptibility loci of ischemic stroke (IS) in a European population. However, conflicting results were obtained in subsequent replication analysis. miR-200c, located on chromosome 12p13, was found to have a neuroprotective effect on ischemia. Our aim of this study was to investigate the association of the rs12425791, rs11833579 and rs12904 in the binding site of miR-200c with the risk of IS. The rs12425791, rs11833579, and rs12904 were genotyped using a TaqMan allelic discrimination assay. The results were verified by Sanger sequencing. We found that the rs12904 AG/GG genotypes and G allele were associated with a decreased risk of IS (AG/GG vs. AA: adjusted OR = 0.64; 95% CI, 0.44-0.95; G vs. A: adjusted OR = 0.65; 95% CI, 0.46-0.93). The combined genotypes of the rs11833579AG/AA and rs12904AG/GG were also associated with a reduced risk of IS (OR = 0.65; 95% CI, 0.46-0.93). These findings suggest that the rs12904 may have a jointly protective effect against the risk of IS.

Association between polymorphisms in the promoter region of miR-17-92 cluster and systemic lupus erythematosus in a Chinese population.

The aim of this study was to investigate the association of genetic polymorphisms in the promoter region of miR-17-92 with systemic lupus erythematosus (SLE). The gene polymorphism was analysed using SNaPshot in 312 SLE patients and 396 controls. Relative expression of miR-17-92 was measured by quantitative real-time PCR. Association was found between rs9515692 and a decreased risk of SLE (CT vs CC: OR = 0.65, 95%CI, 0.46-0.92, P = .014; CT+TT vs CC: OR = 0.64, 95%CI, 0.46-0.90, P = .009; T vs C: OR = 0.69, 95%CI, 0.52-0.92, P = .010, respectively). Haplotype analysis showed that C-G-G, C-A-A haplotypes were associated with an increased SLE risk (OR=4.46, 95%CI, 2.17-9.17, P < 0.001; OR=2.33, 95%CI, 1.44-3.76, P < 0.001, respectively). T allele and CT+TT genotypes in rs9515692 were associated with decreased risk of anti-dsDNA in SLE (CT+TT vs CC: OR = 0.42, 95%CI = 0.24-0.72, P = .002; T vs A: OR = 0.49, 95%CI = 0.31-0.79, P = .003). Moreover, rs9515692 CT+TT genotypes had a higher level of miR-17 as compared to CC genotype (P = .017). These findings suggest that the rs9515692 CT+TT genotypes were a protective factor for the susceptibility of SLE, probably by increasing the expression of miR-17.

Association of interleukin 13 gene polymorphisms and plasma IL 13 level with risk of systemic lupus erythematosus.

Interleukin (IL) 13 plays a critical role in inflammatory diseases, including systemic lupus erythematosus (SLE). This study aims to explore the potential association of IL-13 polymorphisms with the risk of SLE. We genotyped IL-13 rs20541, rs848 and rs1295686 using Snapshot SNP genotyping assays. Plasma IL-13 level was determined by enzyme-linked immunosorbent assay (ELISA). We found that rs20541 was associated with increased risk of SLE (CT vs. CC: adjusted OR=1.43, 95%CI, 1.04-1.99, P=.030; TT vs. CC: adjusted OR=1.73, 95%CI, 1.10-2.73, P=.018; CT/TT vs. CC: adjusted OR=1.50, 95%CI, 1.10-2.04, P=.010; T vs. C adjusted OR=1.34, 95%CI, 1.08-1.93, P=.031). CT and TT genotypes in rs20541 were associated with increased risk of renal disorder in SLE (CT vs. CC: adjusted OR=1.97, 95%CI, 1.18-3.28, P=.009; TT vs. CC: adjusted OR=2.42, 95%CI, 1.22-4.77, P=.011). Moreover, The concentration of IL-13 was significantly elevated in rs20541 CT/TT genotypes compared with CC genotype (P<.001). These results suggest that rs20541 CT/TT genotypes may be a risk factor for SLE, probably by increasing the level of IL-13.

Association study of CD154 polymorphisms and serum CD154 level with systemic lupus erythematous in Chinese population.

The aim of this study was to investigate the association of three polymorphisms of CD154 with risk of SLE in Chinese population. The study population comprised 770 Chinese individuals, including 350 SLE patients and 420 healthy controls. The gene polymorphism was measured using Snapshot SNP genotyping assays and confirmed by sequencing. Serum CD154 (sCD154) level was measured by ELISA. Compared with control group, sCD154 levels were significantly increased in case group (P < 0.001). The minor C allele of rs1126535 was associated with a significantly increased risk of SLE as compared to the major T allele (P < 0.001). Furthermore, an increased frequency of C-G-A haplotype was also detected in case group which associated with an increased risk of SLE (P = 0.009). Notably, patients carrying rs1126535CT/CC genotypes had a higher sCD154 level compared with that carrying rs1126535TT genotype (P < 0.05). Unfortunately, analyses on the association between rs1126535 and several clinical manifestations of SLE failed to find any significant results. In conclusion, these results indicated that CD154 gene polymorphisms may associate with the risk of SLE and may play regulation role in the expression of sCD154 in SLE patients.

The Association of Growth Differentiation Factor-15 Gene Polymorphisms with Growth Differentiation Factor-15 Serum Levels and Risk of Ischemic Stroke.

BACKGROUND: Current evidence shows that growth differentiation factor-15 (GDF-15) plays an important role in the progression of ischemic stroke (IS). The aim of this study was to investigate the association between 3 single-nucleotide polymorphisms of the GDF-15 gene and IS susceptibility in the Chinese population. MATERIALS AND METHODS: The study subjects comprised 601 Chinese individuals, including 298 stroke patients and 303 age- and gender-matched healthy controls. The polymorphisms were measured using snapshot single-nucleotide polymorphism genotyping assays and confirmed by sequencing. Serum GDF-15 (sGDF-15) levels were measured by enzyme-linked immunosorbent assay. RESULTS: The distribution of rs1804826G/T polymorphism was significant different between the 2 groups (P < .05). Compared with the rs1804826 G allele, the rs1804826 T allele was significantly associated with an increased risk of IS (P < .05). Haplotype analyses showed that the T-T-G haplotype was significantly associated with an increased risk of IS (odds ratio = 1.671, 95% confidence interval = 1.231-2.268; P = .001). Compared with the normal controls, the sGDF-15 levels were significantly increased in stroke patients (P < .001). Besides, patients carrying rs1804826 GT/TT genotypes had higher sGDF-15 levels compared with those carrying GG genotypes (P < .05). CONCLUSIONS: The GDF-15 gene rs1804826G/T polymorphism and sGDF-15 levels are associated with IS in the Chinese population. Our data indicate that the GDF-15 gene may play a role in the development of IS.

A SNP in 5' untranslated region of CD40 gene is associated with an increased risk of ischemic stroke in a Chinese population: a case-control study.

Cluster of differentiation 40 (CD40), the receptor for CD154, is a member of the tumor necrosis factor (TNF) receptor superfamily. Several studies have been conducted to investigate the effect of the CD40 rs1883832 polymorphism on atherosclerotic disease in different population; however, inconsistent results were obtained. In this study, we investigated the association of four polymorphisms (rs1883832, rs13040307, rs752118 and rs3765459) of CD40 gene and their effect on CD40 expression with the risk of ischemic stroke (IS) in a Chinese population. Three hundred and eighty patients with IS and 450 control subjects were included in the study. The CD40 polymorphisms were discriminated by Snapshot SNP genotyping assay. Serum soluble CD40 (sCD40) levels were detected by ELISA. We found that the rs1883832CT and rs1883832TT genotypes were associated with an increased risk of IS compared with the rs1883832CC genotype (OR = 1.42, 95% CI: 1.03-1.95, p = 0.030 and OR = 1.91, 95% CI: 1.29-2.82, P = 0.001, respectively), and the rs1883832T allele was associated with a significantly increased risk of IS compared with rs1883832C allele (OR = 1.40, 95% CI: 1.15-1.70, P = 0.001). Elevated serum sCD40 levels were observed in patients with IS compared with the control gropu (P < 0.01). Individuals carrying the rs1883832TT or rs1883832CT genotypes showed significantly higher sCD40 levels compared with the rs1883832CC genotype in the IS group [(64.8 ± 25.4 pg/mL, TT = 94); (63.9 ± 24.3 pg/mL, CT = 185) vs (53.3 ± 22.5 pg/mL, CC = 101), P < 0.01]. The TCCA haplotype was associated with an increased risk of IS compared with the control group (OR = 2.10, 95% CI: 1.23-3.58, p = 0.005). However, we did not find a significant association between the other three polymorphisms and IS risk. In conclusion, after a comprehensive comparison with other studies, we confirmed that the rs1883832T allele but not the rs1883832C allele is associated with an increased risk of IS. The rs1883832 polymorphism may exert influences on abnormal CD40 expression in IS patients among the Chinese population.

Platelet to Lymphocyte Ratio in Polymyositis as a Marker of Disease Activity.

BACKGROUND: Platelet to lymphocyte ratio (PLR) has been regarded as a parameter in assessing systemic inflammation. Polymyositis (PM) is a rare connective tissue diseases characterized by chronic muscle inflammation, which led to a hypothesis with respect to PLR in PM patients. Therefore, it is reasonable to investigate the relationship between PLR and PM. METHODS: The present study included 46 newly diagnosed PM patients and 128 healthy subjects as controls. The muscle weakness of PM patients was measured using the manual muscle test (MMT) to evaluate disease activity in patients with PM. RESULTS: Neutrophil to lymphocyte ratio (NLR) and PLR were higher in patients with PM compared with healthy controls (4.1 ± 1.32 vs. 1.6 ± 0.58, p < 0.001, 158.4 ± 86.39 vs. 103.8 ± 29.82, p < 0.001). PLR was positively correlated with NLR, ESR, and platelet counts (r = 0.392, p = 0.008, r = 0.422, p = 0.020, r = 0.366, p < 0.001), and negatively with lymphocyte counts (r = -0.872, p < 0.001) in patients with PM. Interesting, a reverse correlation between PLR and MMT score was observed in patients with PM (r = -0.383, p = 0.010). However, there was no correlation between NLR and MMT score (r = -0.266, p = 0.074). In logistic regression analysis, PLR was independently associated with PM after adjustment for age, gender, ESR, lymphocyte counts, neutrophil counts, leukocyte counts, and NLR. The resulting odds ratio (OR) and 95% confidence interval (95% CI) were 1.017 (95% CI 1.003 - 1.031; p = 0.015) for PLR. CONCLUSIONS: Our research suggests that PLR is associated with PM, and PLR may be used to estimate disease activity of PM patients.

The association of interleukin-31 polymorphisms with interleukin-31 serum levels and risk of systemic lupus erythematosus.

Interleukin-31 (IL-31) is the most recently discovered member of the gp130/IL-6 cytokine family which is produced mainly by activated Th2 cells. IL-31 was proved to play a crucial role in autoimmune and inflammatory diseases such as atopic dermatitis, asthma, cutaneous T cell lymphomas, Kawasaki disease and allergic rhinitis. Previous studies have identified that IL-31 could significantly induce the release of proinflammatory cytokines IL-6. Moreover, a large number of studies have shown that IL-6 plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, up to date, no study to data was reported on the relationship between IL-31 and SLE. Therefore, in the present study, we investigated the association between IL-31 polymorphisms and its serum levels with the risk of SLE in a Chinese population. We analyzed two single nucleotide polymorphisms of IL-31 gene rs7977932 C/G and rs4758680 G/T in 190 patients with SLE and 250 age- and sex-matched controls, using polymerase chain reaction-single base extension and DNA sequencing methods. Soluble IL-31 (sIL-31) levels were measured by ELISA. From this study, we found that there were significant differences in the genotype and allele frequencies of IL-31 gene rs7977932 C/G polymorphism between the group of patients with SLE and the control group (P < 0.05). sIL-31 levels were increased in patients with SLE compared with controls (P < 0.01). Moreover, genotypes carrying the IL-31 rs7977932 G variant allele were associated with increased IL-31 levels compared to the homozygous wild-type genotype in patients with SLE. The rs7977932 C/G polymorphism of IL-31 gene and its sIL-31 levels were associated with SLE in the Chinese population. Our data suggest that IL-31 gene may play a role in the development of SLE.

Association of CD40 polymorphisms and haplotype with risk of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that is caused by genetic and environmental factors. Current evidence shows that the CD40-CD40L system plays a crucial role in the development, progression and outcome of SLE. CD40, which stimulates lymphocyte proliferation and differentiation, is an important immunomodulator and is expressed in the thyroid follicular cells as well as antigen-presenting cells. The aim of the present study was to investigate whether CD40 gene polymorphism confers susceptibility to SLE and its impact on CD40 expression in Chinese. We analyzed four single nucleotide polymorphisms of CD40 gene rs1883832C/T, rs13040307C/T, rs752118C/T, and rs3765459G/A in 205 patients with SLE and 220 age- and sex-matched controls, using Snapshot SNP genotyping assays and DNA sequencing method. Soluble CD40 (sCD40) levels were measured by ELISA. There were significant differences in the genotype and allele frequencies of CD40 gene rs1883832 C/T polymorphism between the group of patients with SLE and the control group (P < 0.05). sCD40 levels were increased in patients with SLE compared with controls (P < 0.01). Moreover, genotypes carrying the CD40 rs1883832 T variant allele were associated with increased CD40 levels compared with the homozygous wild-type genotype in patients with SLE. The rs1883832 C/T polymorphism of CD40 and its sCD40 levels were associated with SLE in the Chinese population. These data suggest that CD40 gene may play an essential role in the development of SLE.

The association of CD40 polymorphisms with CD40 serum levels and risk of systemic lupus erythematosus.

BACKGROUND: Current evidence shows that the CD40-CD40 ligand (CD40-CD40L) system plays a crucial role in the development, progression and outcome of systemic lupus erythematosus (SLE). The aim of this study was to investigate whether a CD40 gene single nucleotide polymorphism (SNP) is associated with SLE and CD40 expression in the Chinese population. We included controls (n = 220) and patients with either SLE (n =205) in the study. METHODS: The gene polymorphism was measured using Snapshot SNP genotyping assays and confirmed by sequencing. We analyzed three single nucleotide polymorphisms of CD40 gene rs1883832C/T, rs1569723A/C and rs4810485G/T in 205 patients with SLE and 220 age-and sex-matched controls. Soluble CD40 (sCD40) levels were measured by ELISA. RESULTS: There were significant differences in the genotype and allele frequencies of CD40 gene rs1883832C/T polymorphism between the group of patients with SLE and the control group (P < 0.05). sCD40 levels were increased in patients with SLE compared with controls (P < 0.01). Moreover, genotypes carrying the CD40 rs1883832 C/T variant allele were associated with increased CD40 levels compared to the homozygous wild-type genotype in patients with SLE. The rs1883832C/T polymorphism of CD40 and its sCD40 levels were associated with SLE in the Chinese population. CONCLUSIONS: Our results suggest that CD40 gene may play a role in the development of SLE in the Chinese population.

Association of interleukin-8 gene polymorphisms with the risk of hepatocellular carcinoma.

Interleukin-8 (IL8) polymorphisms have been implicated in several cancers, but their roles in the pathogenesis of hepatocellular carcinoma (HCC) are largely unknown. The present study was designed to explore the association between IL8 polymorphism and the risk of HCC in a Chinese population. Four single nucleotide polymorphisms (SNPs) of the IL8 gene -251A/T, +781C/T, -353A/T and +678T/C were analyzed in 205 HCC patients and 208 healthy controls in a Chinese population. Serum levels of IL8 were detected in HCC patients and healthy controls. The association between IL8 polymorphisms and HCC risk was measured using the adjusted odds ratios (OR) and their 95% confidence intervals (CI) from multiple logistic regression analysis. Haplotype analysis and gene-environment interaction analysis was also performed. The serum level of IL8 was significantly higher in HCC patients compared with healthy controls (P < 0.001). After adjusting for confounding factors, no significant associations were found between -251A/T, +781C/T, -353A/T and +678T/C and HCC risk (all P > 0.05). Haplotype analysis showed that A(251)-C(781)-A(353)-C(678) conferred decreased risk of HCC onset (adjusted OR 0.31, 95% CI 0.13-0.77). No significant interaction effects were found between the four SNPs and HBV infection, cirrhosis, gender smoking and alcohol consumption (all P > 0.05). No association between -251A/T, +781C/T, -353A/T and +678T/C of the IL8 gene and the risk of HCC was found in this Chinese population, and the SNPs did not display any interaction with several environmental factors with regard to HCC risk. However, it appears that A(251)-C(781)-A(353)-C(678) is perhaps a protective haplotype for HCC.

The association of L-selectin polymorphisms with L-selectin serum levels and risk of ischemic stroke.

L-selectin is a member of the selectin family of cell adhesion molecules which are important in the transient attachment of leukocytes to endothelial cells, which plays a role in inflammation processes and is one of the earliest events in the pathogenesis of atherosclerosis. No studies have examined the association of this polymorphism with ischemic stroke. Therefore, we investigated that L-selectin gene polymorphism and its soluble level are associated with ischemic stroke in Chinese population. We analyzed single nucleotide polymorphisms of L-selectin gene Pro213Ser (P213S) in 265 patients with ischemic stroke and 280 age and sex matched controls, using PCR-RFLP and DNA sequencing method, while soluble L-selectin levels were measured by ELISA. There were significant differences in the genotype and allele frequencies of L-selectin gene P213S polymorphism between the group of patients with ischemic stroke and the control group (P < 0.05). Soluble L-selectin levels were increased in patients with ischemic stroke compared with controls (P < 0.01). Moreover, The P213S polymorphism of L-selectin was significantly associated with sL-selectin levels, the serum levels of L-selectin PP genotype carriers was significantly higher than no carriers in patients with ischemic stroke (P < 0.05). The P213S polymorphism of L-selectin and its sL-selectin levels are associated with ischemic stroke in Chinese population. Our data suggests that L-selectin gene may play a role in the development of ischemic stroke.

Regional and age difference of human rabies prevalence of the past fourteen years in China.

OBJECTIVE: The aim of this study is to describe the epidemiological characteristics about regional and age difference of human rabies in the past fourteen years in China, and provide a reliable epidemiology basis for further control and prevention of human rabies. METHODS: The database of "China Public Health Science Data Center" affiliated Chinese CDC was searched with the key words of "rabies" or "epidemiology" or "morbidity" or "mortality" from 2004 to 2018 and the corresponding data about human rabies cases was collected referred to regional and age difference for describing the epidemiological characteristics of human rabies. RESULTS: In this study, a total of nearly 26,315 rabies cases (1754 ± 253) and 25,691 rabies-related deaths (1712 ± 255) (Mean ± SE) were reported, and a decreasing trend about the morbidity and mortality of human rabies existed from 0.2039 and 0.2039 (1/100,000) in 2004 to 0.0304 and 0.0295 in 2018. Otherwise, regional difference of human rabies prevalence significantly existed, and juvenile and middle-aged population especially in 50-60 years old were more easily attacked and infected with rabies (all p < 0.05). CONCLUSION: This study proved that human rabies still is a major public health problem in China though a decreasing trend about the morbidity and mortality of human rabies existed in the past fourteen years.

A Functional Polymorphism in HIF-3α Is Related to an Increased Risk of Ischemic Stroke.

Hypoxia-inducible factor-3α (HIF-3α), a member of HIF family, can mediate adaptive responses to low oxygen and ischemia. It is believed that HIF plays crucial roles in stroke-related diseases. However, there are no reports on the association between HIF-3α genetic variants and ischemic stroke (IS) susceptibility. Therefore, we examined the association between HIF-3α gene polymorphisms (rs3826795, rs2235095, and rs3764609) and IS risk. The study population included 302 controls and 310 patients with ischemic stroke. Three polymorphisms in HIF-3α (rs3826795, rs2235095, and rs3764609) were genotyped using SNPscan technique. Our study showed a strong association of rs3826795 in HIF-3α with the risk of IS. The genotype and allele frequencies were shown to differ between the two groups. The rs3826795 in an intron of HIF-3α was related to a prominent increased IS risk (AA vs GG adjusted odd ratio [OR], 2.21; 95% confidence intervals [95% CI], 1.10-4.44; P = 0.03; AA vs AG/GG OR = 1.74, 95% CI, 1.02-2.97, P = 0.04; A vs G OR = 1.48, 95% CI, 1.05-2.07, P = 0.02). Logistic regression analysis suggested that rs3826795 posed a risk factor for IS in addition to common factors. Furthermore, when compared to controls, increased levels of homocysteic acid and level of non-esterified fatty acid were found in the cases (P < 0.01). However, no significant association was found between rs2235095 or rs3264609 and IS risk. These findings indicated that the rs3826795 polymorphism may be a potential target for predicting the risk of IS.

Dissecting Efficacy and Metabolic Characteristic Mechanism of Taxifolin on Renal Fibrosis by Multivariate Approach and Ultra-Performance Liquid Chromatography Coupled With Mass Spectrometry-Based Metabolomics Strategy.

Taxifolin (TFN) is an important natural compound with antifibrotic activity; however, its pharmacological mechanism is not clear. In this study, our aim is to gain insight into the effects of TFN and its potential mechanisms in unilateral ureteral obstruction (UUO) animal model using metabolomics approach to identify the metabolic biomarkers and perturbed pathways. Serum metabolomics analysis by UPLC-Q-TOF/MS was carried out to discover the changes in the metabolic profile. It showed that TFN has a significant protective effect on UUO-induced renal fibrosis and a total of 32 potential biomarkers were identified and related to RF progression. Of note, 27 biomarkers were regulated by TFN treatment, which participate in eight metabolic pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, and phenylalanine metabolism. It also showed that metabolomics was a promising strategy to better dissect metabolic characteristics and pharmacological mechanisms of natural compounds by multivariate approach and ultra-performance liquid chromatography coupled with mass spectrometry.

Association of variants in the interleukin-27 and interleukin-12 gene with nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is multifactorial, and the genetic background may be a crucial etiologic factor. Interleukin-12 (IL-12) is a multifunctional cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. Interleukin-27 (IL-27) is a novel IL-12 family member, the present studies demonstrate that IL-27 mediates potent antitumor activity. Variations in the DNA sequence in the IL-12 and IL-27 gene may lead to altered cytokines production and/or activity, and so this can modulate an individual's susceptibility to NPC. To test this hypothesis, we investigated the relationship of IL-12 and IL-27 gene polymorphisms and NPC in a Chinese population. We analyzed single nucleotide polymorphisms (SNPs) of IL-12 gene 16974 A/C and IL-27 gene -964 A/G, 2905 T/G, 4730 T/C in 302 patients with NPC and 310 age- and sex-matched controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods. There were significant differences in the genotype and allele distribution of 16974 A/C polymorphism of the IL-12 gene among cases and controls. The 16974 CC and AC genotypes were associated with a significantly increased risk of NPC as compared with the 16974 AA genotypes (OR = 2.225, 95% CI 1.395-3.549, P = 0.001 and OR = 1.834, 95% CI 1.239-2.716, P = 0.002, respectively). The 16974 C allele was associated with a significantly increased risk of NPC as compared with the 16974 A allele (OR = 1.334, 95% CI 1.065-1.670, P = 0.012). However, genotype and allele frequencies of the IL-27 gene -964 A/G, 2905 T/G, 4730 T/C polymorphisms in NPC patients were not significantly different than that in healthy controls (P > 0.05). Our data suggest that IL-12 gene may play a role in the development of NPC.