Association of<i> NLRP1</i> and<i> NLRP3</i> Polymorphisms with Psoriasis Vulgaris Risk in the Chinese Han Population

Pei, Yu; Hao, Siyu; Zheng, Hewei; Zhao, Xueying; Li, Yuzhen

doi:10.1155/2018/4714836

Cited by 20 publications

(20 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A study containing 1086 T1D cases and 3273 controls in Norway has demonstrated a significant association between the NLRP1 gene and T1D [13], while another two studies conducted in Poland and Northeast Brazil did not find such association [14, 15]. Our results showed that rs11651270 was significantly associated with T1D while another study confirmed that it was not related to psoriasis vulgaris [33]. Although we did not find a significant association between rs2670660 and T1D, this SNP has been reported to associate with many other autoimmune disorders, such as generalized vitiligo [18], systemic sclerosis [34], and systemic lupus erythematosus [35].…”

Section: Discussionsupporting

confidence: 52%

Polymorphisms in NLRP1 Gene Are Associated with Type 1 Diabetes

Sun

Xia

Liu

et al. 2019

Journal of Diabetes Research

View full text Add to dashboard Cite

Objective. The aim of this study was to clarify the association of two single-nucleotide polymorphisms (SNPs) (rs11651270 and rs2670660) in the NLRP1 (NLR family pyrin domain containing 1) gene with type 1 diabetes (T1D) in the Chinese Han population. We hypothesize that mutations in the NLRP1 gene may affect the susceptibility to T1D. Materials and Methods. A case control study was designed, and participants fulfilling the diagnostic criteria of classical T1D as well as nondiabetic controls were enrolled in the study. The polymorphisms rs11651270 and rs2670660 were genotyped by polymerase chain reaction (PCR) and Sanger sequencing. Chi-squared test and logistic regression analysis were performed to compare the distributions of the allele and genotype between cases and controls. Kruskal-Wallis one-way ANOVA was used to compare the characteristics of different genotypes in participants with T1D. Results. A total of 510 participants with classical T1D as well as 531 nondiabetic controls were enrolled in the study. The two groups were matched in sex (p=0.418). The age (p<0.001) and BMI (p<0.001) were significantly lower in cases compared to controls. Significantly higher values were observed for fasting plasma glucose (FPG) (p<0.001) and 2 h postprandial plasma glucose (PPG) (p<0.001) in individuals with T1D. Regarding the allelic model, the minor allele C of rs11651270 was significantly associated with lower risk of T1D compared with the T allele (OR=0.714, 95% CI=0.579-0.882). Both rs11651270 and rs2670660 polymorphisms were associated with T1D in the Chinese Han population under a dominant model (OR=0.648, 95% CI=0.503-0.834 and OR=0.716, 95% CI=0.549-0.934, respectively) and an overdominant model (OR=0.663, 95% CI=0.511-0.860 and OR=0.711, 95% CI=0.541-0.935, respectively). Additionally, the polymorphism rs11651270 was also related to T1D in an additive model (OR=0.719, 95% CI=0.583-0.887). Most importantly, when we analyzed the clinical characteristics of T1D individuals with different genotypes, we found that the age of onset with the TT genotype at rs11651270 was younger than those with the other two genotypes (p=0.001). Conclusions. SNPs in the NLRP1 gene were associated with T1D, as well as the age of onset in the Chinese Han T1D individuals. Our study indicated that the NLRP1 gene might play a pivotal role in the etiopathogenesis of T1D and could be applied to genetic screening of T1D in the Chinese Han population.

show abstract

Section: Discussionsupporting

confidence: 52%

Polymorphisms in NLRP1 Gene Are Associated with Type 1 Diabetes

Sun

Xia

Liu

et al. 2019

Journal of Diabetes Research

View full text Add to dashboard Cite

show abstract

“…The activated NLRP3 inflammasome could result in the activation of ASC, caspase-1, and the release of mature IL-1β, and eventually promoted the development of inflammation [13]. Accordingly, the pathogenesis and progress of psoriasis were closely related to TLR7/8-MyD88-NF-κB and NLRP3 pathways [14,15].…”

Section: Introductionmentioning

confidence: 99%

Datura Metel L. Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis and Inhibits Inflammatory Cytokines Production through TLR7/8–MyD88–NF-κB–NLRP3 Inflammasome Pathway

et al. 2019

View full text Add to dashboard Cite

Background: Psoriasis is a chronic, immune-mediated inflammatory skin disease, and the inflammatory response plays an important role in its development and progression. Datura metel L. is a traditional Chinese medicine that exhibited a significant therapeutic effect on psoriasis in our previous study due to its remarkable anti-inflammatory effect. Meanwhile, the mechanism underlying its effects on psoriasis is still unclear. Methods: An imiquimod-induced psoriasis-like dermatitis mouse model was constructed to evaluate the protective effect of the effective part of Datura metel L. (EPD), which was verified by evaluations of the Psoriasis Area and Severity Index (PASI) score. Hematoxylin and eosin (H&E) staining, immunohistochemical examination, enzyme-linked immunosorbent assay (ELISA), and Western blot were used to measure the inflammatory cytokines and the protein expression associated with the Toll-like receptor 7– myeloid differentiation primary response gene 88–nuclear Factor-κB–nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (TLR7/8–MyD88–NF-κB–NLRP3) inflammasome pathway. Results: EPD significantly decreased the PASI, reduced epidermal thickness, and decreased the proliferation and differentiation of epidermal cells in psoriasis-like dermatitis C57BL/6 mice induced by imiquimod (IMQ). Furthermore, EPD reduced the infiltration of CD3+ cells to psoriatic lesions, as well as ameliorated the elevations of intercellular adhesion molecule 1 (ICAM-1) and inhibited the production of imiquimod-induced inflammatory cytokines, including IL-1β, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-23, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and interferon-γ (IFN-γ). Besides, EPD decreased the imiquimod-induced expression levels of TLR7, TLR8, TRAF6, MyD88, p-IKKα, p-IKBα, p-NF-κB, NLRP3, apoptosis-associated speck-like protein contained a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase 1 (caspase-1), and IL-1β. Conclusion: This study demonstrated that EPD exhibited a protective effect on an imiquimod-induced psoriasis mice model by inhibiting the inflammatory response, which might be ascribed to the inhibition of the TLR7/8–MyD88–NF-κb–NLRP3 inflammasome pathway.

show abstract

“…e etiopathogenesis of PsV is multigenic and multifactorial. Like our previous studies, [27] our study had several limitations. First, our sample size was relatively small, which may limit the revelation of true relationships.…”

Section: Discussionmentioning

confidence: 85%

“…CARD8 may be involved in psoriasis development as a genetic marker or a causative polymorphism. Previously, our team identified a relationship between several other genetic polymorphisms and PsV [14,[27][28][29]. We will compile these findings to further explore the relationship between these genes and PsV in the Han population of northeastern China.…”

Section: Resultsmentioning

confidence: 93%

A New Risk Polymorphism rs10403848 of CARD8 Significantly Associated with Psoriasis Vulgaris in Northeastern China

Pei

Liu

Hao

et al. 2020

BioMed Research International

Self Cite

View full text Add to dashboard Cite

Caspase recruitment domain family member 8 (CARD8) is an adaptor molecule that negatively regulates nuclear factor-κB (NF-κB) activation, interleukin (IL)-1β secretion, and apoptosis. These play important roles in the pathogenesis of psoriasis. Genetic variants of CARD8 have been associated with an increased risk of several inflammatory diseases and psoriasis in Europe. However, nothing is known about the association of the polymorphisms of CARD8 and psoriasis vulgaris (PsV) in the Han population of northeastern China. To investigate the potential association between them, we designed a case-control study to genotype four selected single nucleotide polymorphisms (SNPs) using the improved multiplex ligation reaction (iMLDR) method. Model-based single SNP frequentist-test and haplotype association studies were performed to assess the association between SNPs and PsV. The results showed that the intron SNP rs10403848 was significantly associated with PsV (additive model p=0.0418, p′=0.0411, and statistical power 0.1902; heterozygous model p=0.0418, p′=0.0164, and statistical power 0.9406). A potential risk locus of nonsynonymous SNP rs2043211 found in the European population did not show a significant association in our study. We found that the polymorphism rs10403848 in CARD8 is significantly associated with PsV risk in the Han population of northeastern China. CARD8 may be involved in PsV in this population, as in the European population, but a different genetic process should be considered for the heterogeneity of risk loci.

show abstract

Association of NLRP1 and NLRP3 Polymorphisms with Psoriasis Vulgaris Risk in the Chinese Han Population

Cited by 20 publications

References 27 publications

Polymorphisms in NLRP1 Gene Are Associated with Type 1 Diabetes

Polymorphisms in NLRP1 Gene Are Associated with Type 1 Diabetes

Datura Metel L. Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis and Inhibits Inflammatory Cytokines Production through TLR7/8–MyD88–NF-κB–NLRP3 Inflammasome Pathway

A New Risk Polymorphism rs10403848 of CARD8 Significantly Associated with Psoriasis Vulgaris in Northeastern China

Contact Info

Product

Resources

About