20 research outputs found

    Variants in Intron 4 of PD-1 Gene are Associated with the Susceptibility to SLE in an Iranian Population

    Full text link
    BACKGROUND: Programmed cell death protein 1 (PD-1) is a negative co-stimulatory molecule with immunomodulatory properties. Recently, PD-1 gene defects have attracted attention in the pathogenesis of SLE. OBJECTIVE: Here, we assessed the association of PD-1 gene polymorphisms in intron 4 and haplotypes with the susceptibility to SLE. METHODS: Seventy-six SLE patients and 159 healthy controls were included. We screened the polymorphisms by amplifying the intron 4 of the PD-1 gene with the specific primers followed by sequencing. RESULTS: Two distinct SNPs were identified (rs6705653 and rs41386439) within the intron 4 of the PD-1 gene. The AA genotype of +7499 (G/A) SNP was associated with the higher risk of SLE OR=3.31, 95% CI (1.25-8.76), p-value=0.045, while A allele was identified as a risk allele OR=1.75, 95% CI (1.10-2.76), p-value=0.015. However, no significant association was observed between the allele and the genotype frequencies of +7209 (C/T) polymorphic region of the PD-1 gene and susceptibility to SLE. Haplotype analysis showed the significantly higher presence of H2 haplotype (AC; +7499/+7209) OR=1.70, 95% CI (1.24-2.33), p-value=0.0012 in SLE patients. CONCLUSION: To the best of our knowledge, this is the first report of the significant association of PD-1 +7499 (G/A) SNP with the SLE susceptibility and the first detection of both polymorphic loci in a population from Iran. However, more investigations are necessary to confirm these findings

    Oscillation in expression of Adenylyl Cyclase isoforms: new insight to regulation of molecular clock

    Full text link
    Background: Mammalian cells contain a cell-autonomous circadian clock that couples endogenous rhythms with changes of cellular environment. Some recent reports have been shown that circadian clock regulates glucose homeostasis; but, their molecular basis is little understood. Adenylyl Cyclase (AC) is a key enzyme in glucose metabolism. We aimed to investigate circadian mRNA expression of two circadian clock genes Cry1, Cry2, and nine Adenylyl Cyclase isoforms. Methods: MCF7 cell culture shocked using horse serum. Every four hours (over a 48-h period), total RNA was extracted and cDNA was synthesized. Expression level of AC isoforms and Cry genes was evaluated by quantitative RT-PCR. Results: Two AC isoforms; AC3, AC6 showed a circadian expression pattern in which they had a significant correlation with Cry1 and Cry2 transcripts. AC3 isoform was also up-regulated after serum shock. Time lags results indicated that AC3 expression was coincided with Cry2 and leads Cry1 expression. Conclusions: Adenylyl Cyclase isoforms, especially AC3, may play an important role in molecular clock regulation and response to external factors. © 2016 Informa UK Limited, trading as Taylor & Francis Group

    Genetic variation in CYP1A1 and AHRR genes increase the risk of systemic lupus erythematosus and exacerbate disease severity in smoker patients

    Full text link
    Background: Genetic variations of aryl hydrocarbon receptor (AHR) pathway genes could influence the imbalanced immune response to xenobiotics. Therefore, we aimed to investigate the polymorphism of AHR pathway genes in systemic lupus erythematosus (SLE) patients in association with smoking. Methods: Genomic DNA from patients (N = 107) and controls (N = 105) of a population from northeast of Iran was used for genotyping of CYP1A1 T>C (rs4646903) and AHRR C>G (rs2292596) variants. The SLEDAI score and smoking status of the patients were registered. The AHR activity was estimated by CYP1A1 and CYP1B1 gene expression in peripheral blood mononuclear cells (PBMC). Results: The C allele in rs4646903 (odds ratio OR = 2.67) and G allele in rs2292596 (OR = 1.79) SNPs were significantly associated with the increased risk of SLE. The AHR pathway was more active in high-risk CYP1A1/AHRR: C/G haplotype. The most severe disease was observed in smoker patients with high-risk haplotype and both smoking (Exp (β) = 9.5) and high-risk CYP1A1/AHRR (C/G) haplotype (Exp (β) = 3.7) can significantly increase the likelihood of having severe (SLEDAI � 20) SLE disease activity. Conclusion: Our findings indicated the association of xenobiotic-metabolizing genes (CYP1A1, AHRR) polymorphisms with the susceptibility to SLE and disease severity regarding the smoking background, suggesting the interaction of gene and environmental risk factors in SLE pathogenesis. © 2021 Wiley Periodicals LL

    Interleukin 10 gene promoter polymorphisms (rs1800896, rs1800871 and rs1800872) and haplotypes are associated with the activity of systemic lupus erythematosus and IL10 levels in an Iranian population

    Full text link
    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unknown aetiology. According to the role of interleukin 10 (IL10) in SLE pathogenesis, the genetic alterations in its promoter region could be associated with elevated IL10 levels and exacerbated disease. Here, we investigated the association of genotype and haplotype frequencies of three IL10 gene promoter polymorphisms with susceptibility to SLE, IL10 plasma levels and disease activity of patients in an Iranian population. A total of 116 SLE patients and 131 healthy subjects were enrolled. The PCR-RFLP technique was used to detect IL10 promoter genotypes at the positions of �1082 (G/A), �819 (C/T) and �592 (C/A) in association with IL10 plasma levels and SLEDAI scores. The GG genotype of �1082 polymorphism was associated with the increased risk of SLE OR = 2.65, 95% CI (1.21�5.82), p-value = 0.046. The CC genotype in �819 region was associated with SLE susceptibility OR = 3.38, 95% CI (1.26�9.07), p-value = 0.034 and C allele was introduced as risk allele OR = 1.86, 95% CI (1.15�3.01), p-value = 0.009 in this region. IL10 plasma levels were overexpressed in CC genotype carriers of �592 SNP and decreased in AA genotype carriers of �1082. IL10 was also increased in SLE patients with CGT (�592/�1082/�819) haplotype. The SLEDAI score was higher among CC genotype carriers at the position of �592 and TT genotype carriers at the region of �819. SLEDAI was also elevated among patients with CGC (�592/�1082/�819) and CAC (p = 0.011) haplotypes. The present study suggests that the IL10 �819(C/T), �1082(G/A) and �592(C/A) polymorphisms and the haplotypes are associated with SLE susceptibility, increased disease activity and elevated IL10 levels. While this is the first time to report such an association in an Iranian population, further studies are needed to confirm these findings. © 2018 John Wiley & Sons Lt

    Intrinsic toughening and stable crack propagation in hexagonal boron nitride

    Full text link
    If a bulk material can withstand a high load without any irreversible damage (such as plastic deformation), it is usually brittle and can fail catastrophically1,2. This trade-off between strength and fracture toughness also extends into two-dimensional materials space3–5. For example, graphene has ultrahigh intrinsic strength (about 130 gigapascals) and elastic modulus (approximately 1.0 terapascal) but is brittle, with low fracture toughness (about 4 megapascals per square-root metre)3,6. Hexagonal boron nitride (h-BN) is a dielectric two-dimensional material7 with high strength (about 100 gigapascals) and elastic modulus (approximately 0.8 terapascals), which are similar to those of graphene8. Its fracture behaviour has long been assumed to be similarly brittle, subject to Griffith’s law9–14. Contrary to expectation, here we report high fracture toughness of single-crystal monolayer h-BN, with an effective energy release rate up to one order of magnitude higher than both its Griffith energy release rate and that reported for graphene. We observe stable crack propagation in monolayer h-BN, and obtain the corresponding crack resistance curve. Crack deflection and branching occur repeatedly owing to asymmetric edge elastic properties at the crack tip and edge swapping during crack propagation, which intrinsically toughens the material and enables stable crack propagation. Our in situ experimental observations, supported by theoretical analysis, suggest added practical benefits and potential new technological opportunities for monolayer h-BN, such as adding mechanical protection to two-dimensional devices.s J.L., Y.Y., H.G. and B.N. gratefully acknowledge financial support by the US Department of Energy, Office of Basic Energy Sciences, under grant number DE-SC0018193. The simulations were performed on resources provided by the Extreme Science and Engineering Discovery Environment through grant MSS090046 and the Center for Computation and Visualization, Brown University
    corecore